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Abstract
Lecithin is a naturally occurring mixture of the diglycerides of stearic, palmitic, and oleic acids, linked to the choline ester of phosphoric acid, commonly called phosphatidylcholine. Hydrogenated Lecithin is the product of controlled hydrogenation of Lecithin. Bilayers of these phospholipids in water may form liposomes, a spherical structure in which the acyl chains are inside and not exposed to the aqueous phase. Lecithin and Hydrogenated Lecithin are used in a large number of cosmetic formulations as skin conditioning agents-miscellaneous and as surfactant-emulsifying agents. Hydrogenated Lecithin is also used as a suspending agent-nonsurfactant. Historical data on concentration of use of Lecithin reveals that 0.1% to 1.0% is the concentration range most frequently seen, with concentrations up to 50% reported for two moisturizing products. A solution of 65% Lecithin is currently reported to be used at concentrations up to 3% in cosmetics. Nonocclusive application of Lecithin-containing liposomes to murine skin resulted in 30% penetration to the subdermis. In piglet skin, the same application resulted in 99% accumulating in the stratum corneum. In general, liposomes are considered effective in capturing other compounds inside their spherical structure and delivering any such captured compound through the skin barrier. As a result, caution should be exhibited in formulating cosmetic products that contain these ingredients in combination with other ingredients whose safety is based on their lack of absorption or where dermal absorption is a concern. Lecithin is virtually nontoxic in acute oral studies, short-term oral studies, and subchronic dermal studies in animals. Lecithin is not a reproductive toxicant, nor is it mutagenic in several assays. In an oral carcinogenicity study, brain neoplasms were found in mice exposed to Lecithin. In a subcutaneous carcinogenicity study, no neoplasms were found in mice and rats exposed to Lecithin. Adverse reactions to Lecithin in a metered-dose inhaler have been reported. Lecithin and Hydrogenated Lecithin were generally nonirritating and nonsensitizing in animal and human skin. Based on the available data, Lecithin and Hydrogenated Lecithin are safe as used in rinse-off cosmetic products; they may be safely used in leave-on products at concentrations up to 15%, the highest concentration tested in clinical irritation and sensitization studies; but the safety of use could not be substantiated in cosmetic products likely to be inhaled. Because of the possibility of formation of nitrosamines, these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed.
... Lecithin are safe as used in rinse-off products, safe for use in leave-on products at concentrations of 15%, and the data are insufficient to determine the safety of use in cosmetic products where Lecithin and Hydrogenated Lecithin are likely to be inhaled; Lecithin and Hydrogenated Lecithin should not be used in cosmetic products in which N-nitroso compounds may be formed. 1 The qualification relating to the formation of N-nitroso compounds was based on concern over N-nitrosation of a potential bacterial metabolite. The 15% concentration limit and the qualification relating to the formation of N-nitroso compounds are, however, no longer applicable, and the available data addressing cosmetics that may be inhaled are sufficient. ...
... Lecithin, for example, is a complex mixture of phosphatides, consisting chiefly of PC, phosphatidylethanolamine, Phosphatidylserine, and Phosphatidylinositol, with varying amounts of triglycerides, fatty acids, and carbohydrates isolated from animal or vegetable sources. 1 In naturally occurring lecithins, the phosphoric acid is attached to the glycerol at the a-position. However, the phosphoric acid moiety can also be attached in the b-position of glycerin, as a by-product of synthesis. ...
... Hydrogenated Lecithin (CAS No. 92128-87-5) is the end product of the controlled hydrogenation of Lecithin. 1 Despite the ionic, or even zwitterionic, natures of these ingredients, these ingredients are mostly insoluble in water. 3 These ingredients typically are waxy, hygroscopic substances that swell in contact with water to form, dependent on their molecular composition and structure, liposomes, micelles, or mixed micelles. ...
The phosphoglycerides considered in this safety assessment are reported to function primarily as skin and hair conditioning agents, emulsifying agents, and surfactants in cosmetic products and are used up to a maximum reported concentration of 50%. Although phospholipids exert physiologic effects, these are not reproduced by application of phospholipid ingredients to the skin. Given the possibility that Lecithin may be derived from animal sources, it should be noted that the Food and Drug Administration does not permit the use of ingredients made from bovine specified risk materials in cosmetic products. The Expert Panel for Cosmetic Ingredient Safety concluded that the 17 phosphoglycerides are safe in the present practices of use and concentration in cosmetics, as described in this safety assessment.
... Nonetheless, the highly penetrant lpd-3 mutant phenotypes may serve as a useful C. elegans model to help understand how BLTP1 mutations contribute to AKS etiology and to develop potential interventions for treating AKS. Indeed, we found that most lpd-3 mutant phenotypes can be rescued by the dietary supplementation of Lecithin, a naturally occurring mixture with highly enriched unsaturated phospholipids (Fiume, 2001;Scott, 2005). Lecithin is present in milk and represents a commonly used dietary supplement known for its excellent bioavailability and safety profiles in humans (Fiume, 2001;Scott, 2005). ...
... Indeed, we found that most lpd-3 mutant phenotypes can be rescued by the dietary supplementation of Lecithin, a naturally occurring mixture with highly enriched unsaturated phospholipids (Fiume, 2001;Scott, 2005). Lecithin is present in milk and represents a commonly used dietary supplement known for its excellent bioavailability and safety profiles in humans (Fiume, 2001;Scott, 2005). Despite this, its potential therapeutic effects in alleviating symptoms of AKS patients remain unknown, but pose a fascinating future research avenue. ...
In eukaryotic cells, lipid transfer can occur at membrane contact sites (MCS) to facilitate the exchange of various lipids between two adjacent cellular organelle membranes. Lipid transfer proteins (LTPs), including shuttle LTP or bridge-like LTP (BLTP), transport lipids at MCS and are critical for diverse cellular processes, including lipid metabolism, membrane trafficking, and cell signaling. BLTPs (BLTP1-5, including the ATG2 and VPS13 family proteins) contain lipid-accommodating hydrophobic repeating β-groove (RBG) domains that allow the bulk transfer of lipids through MCS. Compared with vesicular lipid transfer and shuttle LTP, BLTPs have been only recently identified. Their functions and regulatory mechanisms are currently being unraveled in various model organisms and by diverse approaches. In this review, we summarize the genetics, structural features, and biological functions of BLTP in the genetically tractable model organism C. elegans. We discuss our recent studies and findings on C. elegans LPD-3, a prototypical megaprotein ortholog of BLTP1, with identified lipid transfer functions that are evolutionarily conserved in multicellular organisms and in human cells. We also highlight areas for future research of BLTP using C. elegans and complementary model systems and approaches. Given the emerging links of BLTP to several human diseases, including Parkinson's disease and Alkuraya-Kučinskas syndrome, discovering evolutionarily conserved roles of BLTPs and their mechanisms of regulation and action should contribute to new advances in basic cell biology and potential therapeutic development for related human disorders.
... The anti-dark-spot effect of the α-mangostin-loaded USUC in this study is attributed mainly to inhibition of melanin formation [39]. The beneficial effects of other components in the formula, such as soy lecithin (rich in iso-flavones and amino acid) [22] and virgin coconut oil (rich in short and medium chain fatty acids), that nourish skin may also facilitate brightening and hydrating effects on skin in less time than with conventional formulae [40]. ...
... Factors and levels for the 2 5 factorial design[18,[20][21][22]. ...
If it can be effectively delivered to its site of action, α-mangostin has potential in development of novel cosmeceuticals due to its melanogenesis-blocking activity. The aim of this study was to develop an ultra-small unilamellar carrier system for α-mangostin and to evaluate its effect as an anti-age-spot serum on humans in vivo. The ultra-small unilamellar carrier bases were optimized using a 25 factorial design, with five factors (virgin coconut oil, soy lecithin, Tween 80, and stirring duration and speed) and two levels (low and high); response of droplet size was analyzed using Design Expert 12®. The anti-spot examination was conducted via capturing digital images of the human skin after topical application of an α-mangostin-loaded ultra-small unilamellar carrier at night for two consecutive weeks. The results thereof were analyzed using Motic Live Imaging 3.0 and a standard red, green, and blue score. The optimized serum formula was confirmed with a composition of 2.3% virgin coconut oil, 1% lecithin, and 28.3% Tween 80 (polysorbate 80) at a stirring speed of 1500 revolutions per minute for 15 min. Incorporation of 3% α-mangostin to the optimized base formula produced an ultra-small unilamellar carrier globule size of 16.5 nm, with zeta potential of −25.8 mV and a polydispersion index of 0.445. Physical characterization of an α-mangostin-loaded ultra-small unilamellar carrier comprised 90.94% transmittance, a pH value of 6.5, a viscosity of 38 cP, specific gravity of 1.042 g/mL and 72.46% entrapment efficiency. A transmission electron microscope confirmed spherical nanosized droplets in the system. Topical application of an α-mangostin-loaded ultra-small unilamellar carrier at night for 2 consecutive weeks demonstrated anti-age-spot activity shown through a significant reduction in intensity and area of spots in human volunteers (p < 0.05).
... The average diameter, polydispersity index and zeta potential were determined by means of Photon Correlation Spectroscopy method by using a Zetasizer Ultra (Malvern Panalytical Ltd, Worcestershire, UK). Before the analysis, samples were diluted (1:100) with water to be optically clear and avoid the attenuation of the laser beam by the particles along with the reduction of the scattered light that can be detected [19]. ...
... Even the homogeneity of the vesicles was affected by the amount of lentisk oil incorporated, but with a reverse trend as the lower value of polydispersity index has been found for 30lentisk-liposomes. The zeta potential remained strongly negative, irrespective of the used amount of oil and was mainly due to the negative group of phospholipids at the pH of dispersions, ~5.5 [19]. All tested liposomes incorporated high amount of lentisk oil, which increased as the amount of lentisk oil used for their preparation also increased. ...
Pistacia lentiscus L. is a sclerophyllous shrub capable of growing under harsh climatic conditions especially in the Mediterranean Basin. Different products can be obtained from this plant, such as essential oil, mastic gum or even fixed oil. The last is well known for its flavor which is mainly exploited in the food industry. Additionally, it has been traditionally used in the treatment of skin diseases, but, at the moment, any suitable formulation for skin delivery has been formulated and its biological effects was not deeply confirmed. Given that, in the present study, the lentisk oil has been formulated in liposomes at different concentrations (10, 20, 30 mg/ml) and their physicochemical, technological and main biological properties have been evaluated. Vesicles were prepared by using natural soy lecithin and a green and organic solvent free method, thus obtaining spherical, small (~ 118 nm), homogeneously dispersed (0.27) and highly negatively charged (~ − 62 mV) vesicles. The used amount of oil loaded in liposomes (10, 20, 30 mg/ml) modulated the penetration ability of vesicles in the skin, favoring the deposition of the payload in the deeper strata. The loading in the vesicles potentiated the ability of oil to counteract the damaging effects caused by hydrogen peroxide in keratinocytes and fibroblasts and facilitate their migration in a cell monolayer lesion. Overall findings suggested that the incorporation of lentisk oil in liposomes made from soy lecithin can be an alternative and natural approach to exploit it in pharmaceutical ad cosmetical applications and manufacturing natural products suitable for the treatment of skin lesions.
... Lecithin antioxidant effect, dispersing agent for pigments [409] safe as used in rinse-off products safe for use in leave-on products at concentrations of 15% insufficient data to determine the safety for use in cosmetic products where Lecithin or Hydrogenated Lecithin are likely to be inhaled [409] Malachite Extract a copper complex extracted from the malachite stone, being a powerful free radical scavenger, boosting cellular defenses, offering protection and detoxifying benefits [410] * N Sodium Pyrrolidone Carboxylate skin moisturizing effect [411] safe in cosmetics non-irritating in a reconstructed human epidermis model test using the EpiSkin model [412] Superoxide Dismutase (SOD) reduces UV-induced erythema, free radical scavenger, anti-irritant effect, anti-ageing capacity [413] non-irritating and non-sensitizing [413] Urea humectant, decreases TEWL in normal skin and especially in xerotic skin disorders (AD patients) [414] moisturizing effect, desquamating actions (urea dissolves the intercellular cementing substance in the SC), antimicrobial action [415][416][417] safe as used in cosmetic products [415]. ...
... Lecithin antioxidant effect, dispersing agent for pigments [409] safe as used in rinse-off products safe for use in leave-on products at concentrations of 15% insufficient data to determine the safety for use in cosmetic products where Lecithin or Hydrogenated Lecithin are likely to be inhaled [409] Malachite Extract a copper complex extracted from the malachite stone, being a powerful free radical scavenger, boosting cellular defenses, offering protection and detoxifying benefits [410] * N Sodium Pyrrolidone Carboxylate skin moisturizing effect [411] safe in cosmetics non-irritating in a reconstructed human epidermis model test using the EpiSkin model [412] Superoxide Dismutase (SOD) reduces UV-induced erythema, free radical scavenger, anti-irritant effect, anti-ageing capacity [413] non-irritating and non-sensitizing [413] Urea humectant, decreases TEWL in normal skin and especially in xerotic skin disorders (AD patients) [414] moisturizing effect, desquamating actions (urea dissolves the intercellular cementing substance in the SC), antimicrobial action [415][416][417] safe as used in cosmetic products [415]. ...
This study proposes a review on hyaluronic acid (HA) known as hyaluronan or hyaluronate and its derivates and their application in cosmetic formulations. HA is a glycosaminoglycan constituted from two disaccharides (N-acetylglucosamine and D-glucuronic acid), isolated initially from the vitreous humour of the eye, and subsequently discovered in different tissues or fluids (especially in the articular cartilage and the synovial fluid). It is ubiquitous in vertebrates, including humans, and it is involved in diverse biological processes, such as cell differentiation, embryological development, inflammation, wound healing, etc. HA has many qualities that recommend it over other substances used in skin regeneration, with moisturizing and anti-ageing effects. HA molecular weight influences its penetration into the skin and its biological activity. Considering that, nowadays, hyaluronic acid has a wide use and a multitude of applications (in ophthalmology, arthrology, pneumology, rhinology, aesthetic medicine, oncology, nutrition, and cosmetics), the present study describes the main aspects related to its use in cosmetology. The biological effect of HA on the skin level and its potential adverse effects are discussed. Some available cosmetic products containing HA have been identified from the brand portfolio of most known manufacturers and their composition was evaluated. Further, additional biological effects due to the other active ingredients (plant extracts, vitamins, amino acids, peptides, proteins, saccharides, probiotics, etc.) are presented, as well as a description of their possible toxic effects.
... The erythema scores were zero for both groups indicating good skin safety and tolerance. As phospholipids (lecithin and hydrogenated lecithin) are generally reported as safe and well-tolerated by the skin [80,81]s, investigated formulations looked safe as they were phospholipid-based. Traul and coworkers found that a 30% dispersion of the phospholipids in medium-chain triglycerides is well-tolerated in dermal and cosmeceutical preparations [82]. ...
The objective of the current work was to fabricate, optimize and assess olive oil/phytoso-mal nanocarriers to improve quercetin skin delivery. Olive oil/phytosomal nanocarriers, prepared by a solvent evaporation/anti-solvent precipitation technique, were optimized using a Box-Behnken design, and the optimized formulation was appraised for in vitro physicochemical characteristics and stability. The optimized formulation was assessed for skin permeation and histolog-ical alterations. The optimized formulation (with an olive oil/PC ratio of 0.166, a QC/PC ratio of 1.95 and a surfactant concentration of 1.6%), and with a particle diameter of 206.7 nm, a zeta potential of −26.3 and an encapsulation efficiency of 85.3%, was selected using a Box-Behnken design. The optimized formulation showed better stability at ambient temperature when compared to refrigerating temperature (4 °C). The optimized formulation showed significantly higher skin permeation of quercetin when compared to an olive-oil/surfactant-free formulation and the control (~1.3-fold and 1.9-fold, respectively). It also showed alteration to skin barriers without remarkable toxicity aspects. Conclusively, this study demonstrated the use of olive oil/phytosomal nanocarriers as potential carriers for quercetin-a natural bioactive agent-to improve its skin delivery.
... They have been widely used as solvents, suspending agents, emulsifying agents, and therapeutic agents in various topical creams, microemulsions, and ointments. Fiume et al. conducted extensive safety assessment on phospholipids such as lecithin and showed that even higher concentrations of lecithin are nontoxic and did not lead to skin irritation [45]. Similarly, previous studies have shown that inclusion of a high concentration of propylene glycol did not induce any visible irritation or toxicity after the application of microemulsion for 7 days on the skin of rabbits [46]. ...
This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.
... All formulations contained nano calcium sulphate (promotes rapid healing and aids in tissue regeneration) [1,21], nano copper oxide (promotes angiogenesis and skin extra cellular matrix formation), varying concentrations of poloxamer 40 and chitosan, 0.12 % of soy lecithin (to maintain tissue hydration and aid in tissue repair [33,34]), 0.9 % of sodium chloride (maintains isotonicity), and 1 % glycerol (humectant that absorbs exudate from wounds and prevents its pooling in areas surrounding the wound). ...
Initial care and treatment of burn injuries significantly influence their healing and appearance. The apt treatment for a burn patient normally depends upon the severity of the burn. This study was intended for the development of thermo-responsive formulations for the emergency management of burns prior to hospitalization.
Nano calcium sulfate was prepared by probe sonication and nano copper oxide by thermal decomposition method and subsequently evaluated for particle size and poly-dispersity index. Formulations were prepared with 100 ppm of nano calcium sulphate, nano copper oxide and thermoresponsive polymers such as Poloxamer-407/ Chitosan/chitosan + Sodium β -glycerophosphate in different ratios. The products were evaluated for pH, viscosity and gelation time and those formulations which exhibited optimum viscosity, pH and gelation time were sterilized and evaluated for elemental content, skin irritation potential and in vivo burn healing activity.
Nano calcium sulfate and nano copper oxide exhibited an average particle size of 220 nm and 273 nm correspondingly. SEM-EDX of selected formulations showed intense peaks of calcium and copper in all formulations. Acute dermal irritation study carried out on rabbits showed that the formations were non-irritant in nature. The percentage of wound contraction was greater in burn wounds treated with the formulation containing poloxamer-407 when compared to commercial Silverex™ ionic gel and the control group. The healing actvity of the thermoresponsive formulations was supported by histopathological studies.
Nano calcium sulfate and nano copper oxide incorporated thermo-responsive formulations with burn wound healing activity were developed successfully.
... On the other hand, Lipoid P75® should be expected to have less toxicity since lecithin is a natural component of cell membranes [46]. However, cases of acute toxicity have been reported when lecithin is used in high concentrations (> 15%) [47]. However, the lecithin used for LNC/ triam, either in solution or hydrogel, does not exceed 0.45%. ...
Two pegylated lipid nanocapsules for triamcinolone transdermal delivery were designed. Both present a size close to 50 nm and a single monomodal distribution in particle size (PI < 0.2), with a zeta potential of - 20 ± 2 and + 18 ± 1, respectively. The triamcinolone encapsulation efficacy varied between 68 and 80%. They proved to be stable under storage conditions (4 °C) for at least 6 months and at a physiological temperature, using different media, for 48 h. Also, they were shown not to affect cell viability at the concentrations used. For ex vivo transdermal experiments, newborn pig skin was used. With respect to the triamcinolone transdermal penetration, the nanocapsules were demonstrated to have an absorption promoting effect, both when the drug nanocapsules were in solution or loaded into the hydrogel, quantifying between 2 and 15 times more absorbed drug than the control. In addition, regarding the triamcinolone retained in the skin, it is observed that lipid nanocapsules act as triamcinolone promoters when the nanosystems were in solution and when they were included in the hydrogel. This vehicle showed a greater triamcinolone reservoir effect in comparison to the nanocapsules, proving to be a good vehicle to formulate triamcinolone transdermal delivery.
... It is important to mention that the vehicle does not have to be inert, it can also have biological properties with the ability to contribute to the overall effect [25]. For instance, lecithin is widely used as an emulsifier in cosmetic formulations, which has a moisturizing effect, contributing to skin hydration [28]. ...
Flawless skin is the most universally desired human feature" is an iconic statement by Desmond Morris. Skin indicates one s health and is so important that it affects a person's emotional and psychological behavior, these facts having propelled the development of the cosmetics industry. It is estimated that in 2023, this industry will achieve more than 800 billion dollars. This boost is due to the development of new cosmetic formulations based on nanotechnology. Nanocarriers have been able to solve problems related to active ingredients regarding their solubility, poor stability, and release. Even though nanocarriers have evident benefits, they also present some problems related to the high cost, low shelf life, and toxicity. Regulation and legislation are two controversial topics regarding the use of nanotechnology in the field of cosmetics. In this area, the U.S. FDA has taken the lead and recommended several biosafety studies and post-market safety evaluations. The lack of a global definition that identifies nanomaterials as a cosmetic ingredient is a hindrance to the development of global legislation. In the EU, the legislation regarding the biosafety of nanomaterials in cosmetics is stricter. "The cost is not the only important issue, safety and the application of alternative testing methods for toxicity are of crucial importance as well".
... Soybean extracts are used as a component of extenders, especially during long-term storage (Salamon and Maxwell, 2000). In recent decades, soybean lecithin was reported to have neither a cytotoxic effect nor a negative effect on sperm motility has been demonstrated to be safer than egg yolk, and it is used for sperm cryopreservation in different species (Hong et al., 1986;Fiume, 2001). The results of the present study indicated that Tris soybean lecithin-based extender was better than the tris egg yolk based extender in preserving Damascus goat semen. ...
The objective of this study was to evaluate the effect of supplementation of different concentrations of royal jelly (RJ) in Tris-egg yolk (TEY) and Tris-soybean (TSL) extenders on sperm quality of Damascus buck chilled semen. The ejaculates were collected from five bucks using an electroejaculator twice a week during the reproductive season. Semen samples were pooled and diluted in extenders supplemented with RJ (1%, 0,75%, 0,50%, 0,25%) with a final concentration of 150x10 6 spermatozoa/mL and stored for 72 hours. The samples were evaluated for sperm quality parameters, including motility, viability, abnormality, membrane integrity, pH, osmolarity. When the RJ doses were compared among each other, 1% RJ concentration caused an increase in the percentage of abnormal and dead spermatozoa in the TSL extender. In the TEY extender, the control and 0.25% RJ concentration groups had the lowest motility and viability values. Generally, the addition of medium and high doses of RJ in the TEY extender group was found to be beneficial to sperm motility and plasma membrane integrity. Although motility was terminated at the 48th hour in the TEY control and 0.25% RJ groups, other trial groups continued. In conclusion, it was determined that the TSL extender was superior to the short-time storage of the goat spermatozoa in the between-groups evaluation, and the RJ supplementation did not achieve any success during the liquid storage at 4°C in the TSL extender. RESUMEN El objetivo de este estudio fue evaluar el efecto de la suplementación de diferentes concentraciones de jalea real (RJ) en los diluyentes Tris-yema de huevo (TEY) y Tris-soja (TSL) sobre la calidad del semen refrigerado de machos cabríos Damasco. Los eyaculados se recogieron dos veces por semana durante la temporada reproductiva de cinco machos utilizando un electroeyaculador. Las muestras de semen se agruparon y diluyeron en TEY y TSJ suplementados con RJ (1%, 0,75%, 0,50%, 0,25%), a una concentración final de 150x10 6 espermatozoides/ml y se almacenaron durante 72 horas. Las muestras fueron evaluadas para parámetros de calidad como motilidad, viabilidad, anormalidad, integridad de la membrana, pH y osmolaridad. Cuando las dosis de RJ se compararon entre sí, la concentración de RJ al 1% causó un aumento en el porcentaje de espermatozoides anormales y muertos en el extensor de TSL. En el diluyente TEY, el control y los grupos de concentración de 0,25% RJ tuvieron los valores más bajos de movilidad y viabilidad. En general, se encontró que la adición de dosis medias y altas de RJ en el grupo TEY fue beneficiosa para la motilidad de los espermatozoides y la integridad de la membrana plasmática. Aunque la motilidad se terminó a las 48 horas en el control TEY y en los grupos con 0,25% de RJ, en los otros grupos de prueba la motilidad continuó. En conclusión, se determinó que el diluyente TSL fue superior para el almacenamiento a corto plazo de los espermatozoides de macho cabrío en la evaluación entre grupos, y que la suplementación con RJ no logró ningún éxito durante el almacenamiento de líquido a 4°C en el diluyente TSL. source are credited / Este es un artículo de acceso abierto distribuido bajo los términos de la Licencia Creative Commons Attribution, la cual permite el uso irrestricto, la distribución y reproducción en cualquier medio, dando el crédito correspondiente al autor y la fuente original.
... Lipid-based nanocarriers have gained great significance as therapeutic delivery systems for siRNA in the last two decades (Li et al., 2020). Lecithin (LC) is a safe food additive that occurs naturally as a mixture of diglycerides of stearic, palmitic, and oleic acids, linked to the choline ester of phosphoric acid, as in Figure 1 (Fiume, 2001). Polymer-lipid hybrid carriers combine the merits of liposomes and polymers to create a nanoscale, biocompatible, and efficient delivery system for genetic materials (Schäfer et al., 2010;De Jesus and Zuhorn, 2015;Pinnapireddy et al., 2019). ...
Small interfering RNA (siRNA) has received increased interest as a gene therapeutic agent. However, instability and lack of safe, affordable, and effective carrier systems limit siRNA's widespread clinical use. To tackle this issue, synthetic vectors such as liposomes and polymeric nanoparticles have recently been extensively investigated. In this study, we exploited the advantages of reduced cytotoxicity and enhanced cellular penetration of chitosan-phthalate (CSP) together with the merits of lecithin (LC)-based nanoparticles (NPs) to create novel, ellipsoid, non-cytotoxic, tripolyphosphate (TPP)-crosslinked NPs capable of delivering siRNA efficiently. The resulting NPs were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and were found to be ellipsoid in the shape of ca. 180 nm in size, exhibiting novel double-layer shells, with excellent stability at physiological pH and in serum solutions. MTT assay and confocal fluorescence microscopy showed that CSP-LC-TPP NPs are non-cytotoxic and efficiently penetrate cancer cells in vitro. They achieved 44% silencing against SLUG protein in MDA-MB-453 cancer cells and were significantly superior to a commercial liposome-based transfection agent that achieved only 30% silencing under comparable conditions. Moreover, the NPs protected their siRNA cargos in 50% serum and from being displaced by variable concentrations of heparin. In fact, CSP-LC-TPP NPs achieved 26% transfection efficiency in serum containing cell culture media. Real-time wide-field fluorescence microscopy showed siRNA-loaded CSP-LC-TPP NPs to successfully release their cargo intracellularly. We found that the amphoteric nature of chitosan-phthalate polymer promotes the endosomal escape of siRNA and improves the silencing efficiency.
... Lecithin is non-irritating and non-sensitizing to human or animal skin. It has been found that by non-occlusive application in the form of liposomes, 30% of lecithin penetrates the murine skin and up to 99% has accumulated in the piglet skin [49]. Therefore, it can be argued that its penetration into the stratum corneum is high. ...
Abstract: Micro- and nanoemulsions are potential drug solubilizers and penetration enhancersthrough the high surfactant/co-surfactant content. This study aimed to evaluate the influenceof minoxidil (MXD) solubilized in the microemulsions (MEs) on drug release byin vitro/ex vivodiffusion through the semi-permeable membrane Spectra/Por®(Spectrum Laboratory, Gardena, CA,USA) and porcine ear skin. Moreover, a residual amount of drug in the skin after ex vivo diffusionwas evaluated. The reference MER, lecithin-containing MEL, and gelatin-containing MEGwerecharacterized in terms of their size, polydispersity index, density, viscosity, electrical conductivityand surface tension. Based on thein vitrodiffusion, it can be argued that MELslowed down thedrug release, while MERand MEGhave no significant effect compared to the sample, in whichpropylene glycol (PG) was used as a solubilizer. Determination of the residual drug amount in theskin after 6 h of the ex vivo permeation was demonstrated as the most valuable method to evaluatethe effectiveness of the ME’s application. The results indicate that the most optimal MXD permeationenhancers in alginate gel were the natural surfactants containing MEs. MXD solubilization in MEGand MELhad caused more than 5% of the drug remaining in the skin, which is almost a 1.5-foldhigher amount compared to the reference gel.
Citation: Špaglová, M.; Čuchorová, M.; Čierna, M.; Poništ, S.; Bauerová, K. Microemulsions as Solubilizers and Penetration Enhancers for Minoxidil Release from Gels. Gels 2021, 7, 26. https://doi.org/10.3390/gels7010026
... The superiority of SBL in semen extenders may be related to lacking the cytotoxicity of lecithin (Fiume, 2001). However, increasing the level SBL to 2% in the current study impaired post-thawed semen quality. ...
The present study was conducted to demonstrate whether soy lecithin could be used as an alternative to egg yolk (EY) in tris-extender for cryopreservation of APRI rabbit semen. In tris-extender (E1), 18% EY was replaced by 1% (E2), 1.5% (E3), or 2% (E4) SBL (1:4). Semen was evaluated visually after cryopreservation stages and by CASA only post-thawing. Results showed that visual sperm motility, livability, abnormality, acrosome integrity, and membrane integrity were improved (P<0.05) by E3 after all cryopreservation stages. Slow, total progressive, and total motility were the highest (P<0.05), while non-motility and non-progressive motility were the lowest (P<0.05) with E3 compared with other extenders. In comparing with E1, E3 showed the best dynamic sperm parameters, in terms of the highest VCL, STR (P<0.05), VSL (P≥0.05), and the lowest (P<0.05) WOB. Prolificacy of rabbits showed the highest (6.68 kits/doe, P<0.05) by E3 compared with 4.96, 4.72, and 2.8 kits/doe for E1, E2, and E4, respectively. The correlation coefficient was the lowest (r=0.691, P<0.05) between acrosome integrity and litter size, and the highest (r= 0.921, P<0.001) between membrane integrity and prolificacy. Progressive motility and slow motility correlated with pregnancy (r=0.811and r=0.778, P<0.01) and prolificacy (r=0.898, P<0.001 and 0.801, P<0.01). In conclusion, addition of soybean lecithin at a level of 1.5% as an alternative to 18% egg yolk in tris extender may has a beneficial impact on motility parameters of cryopreserved APRI-rabbit spermatozoa, and prolificacy of doe rabbits.
... Accordingly, morphological examination of RPE1 normal human retina cells on light microscope shown in Fig 3A, 3B and 3C, did not show any morphological changes in treated cells using concentration of 100 μg/mL and incubation for 48h, which appeared similar in architecture to negative control. The obtained results agreed with [57,58], who reported the safety of lecithin and date palm pollen. These results revealed the safe use of carrier and DPP nanocapsules which encourage their food applications. ...
The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form. Functional yoghurt fortified with DPP in three forms was prepared and their physicochemical, microstructure, texture and sensory characteristics were assessed. The micro morphology was explored via Scanning Electron Microscope (SEM). Fourier Transform Infrared (FTIR) spectroscopy was employed for functional groups detection. Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC). Cytotoxicity of DPP nanocapsules was evaluated against RPE1 cell line (BJ1). The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g). The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP. Fortification with nanoencapsulated DPP proved to be safe and the recommended form due to the announced positive characteristics. Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (10⁶ CFU/g) and prebiotics represented in DPP forms.
... In fact, other lipidic nanocarriers contain saturated lipids in their structure, which limits the proper application of them in food. Lecithin, as used in the synthesis of liposomes and phytosomes, is a natural compound commonly used in several applications, including food products, such as mayonnaise, and in the level they are used, they are GRAS recommended by the US Food and Drug Administration (FDA) (Lecithin, 2001). There are sufficient reasons indicating that the phytosome is superior to the liposomes in structural integrity as discussed previously in this chapter. ...
Nano-phytosome based delivery systems
... In dogs given labeled dilinoleoyl PC, more than 90% of radioactivity was absorbed from the intestinal lumen within 24 hours (22). Dietary and biliary PC's are hydrolysed by pancreatic phospholipases (cf. ...
Lecithin in dog food Lecithin is soaplike, it seeks the interface of fat and water. Within its structure, lecithin has a fatty-acid region that orients to fat and a phosphate-choline group that aligns with water. Many petfoods declare lecithin as ingredient. Actually, blends of true lecithin, fat-and lecithin-like compounds, named lecithins, are used in petfood. Lecithins are legally defined as technological additives and categorized as emulsifiers (1), substances that help fat and water mix together. Lecithins are diverse oilseed derivatives containing about 20% lecithin (2, 3, Note 1). Their use in wet petfood aims at reducing the occurrence of globs of congealed fat. In dry food production, lecithins are deemed to improve the mixing of dry and fatty ingredients, along with water and steam, prior to cooking and kibble forming. Some dry dog foods assert that added lecithin, that is lecithins, enhances digestion of dietary fat, supports healthier haircoat and, less often, that it sharpens brain and lowers cholesterol. Lecithin is a crucial component of the outer surface of body cells. Bile lecithin contributes to the formation of water-soluble aggregates that carry digested, dietary fat toward intestinal uptake. The dog's liver makes sufficient lecithin so that it is not a required nutrient. Dry food may contain 0.6% lecithin as held by its base ingredients, but creation in the dog's body is equivalent to no less than 3.6%. Added lecithins in dry food normally correspond maximally to 0.2% true lecithin. The four health claims in lecithin advertising lack scientific evidence. Moreover, they can be considered illogical. The amount of lecithin added is minor compared with basal dietary lecithin plus bile lecithin, rendering enhanced miscibility of digested fat and water unlikely. Similar reasoning erodes the other lecithin-related health claims.
... Moreover, Gil et al. (2003) recommended that egg yolk concentration not higher than 5-10% supports frozen-thawed ram semen characteristics when milk-based extenders are used, whereas Bioexcell ® , a free of animal origin additives extender (IMV, L' Aigle, France) which contains 6.4% glycerol, may be alternative to the conventional milk extender that contains 5% egg yolk. Taking into account that soybean lecithin is safer than egg yolk as the risk of microbial contamination is significantly lower (Bousseau et al., 1998) and not any cytotoxic effect of it has been reported (Fiume, 2001), it is widely used as an alternative of egg yolk in ram semen diluents. An improvement of sperm motility, viability and membrane integrity has been referred in soybean concentrations between 1-1.5% (Emamverdi et al., 2013;Forouzanfar et al., 2010). ...
Ram semen cryopreservation contributes to genetic improvement through artificial insemination, eliminates geographical barriers in artificial insemination application and supports the preservation of endangered breeds thus the conservation of biodiversity. Sperm freezing process induces ultrastructural, biochemical and functional changes of spermatozoa. Especially, spermatozoa's membranes and chromatin can be damaged, sperm membranes' per-meability is increased, hyper oxidation and formation of reactive oxygen species takes place, affecting fertilizing ability and subsequent early embryonic development. Aiming to improve ram frozen-thawed semen's fertilizing capacity, many scientific investigations took place. Among them the composition of semen extenders, was a main point of interest. Semen preservation extenders regulate and support an environment of adequate pH and buffering capacity to protect spermatozoa from osmotic and cryogenic stress. Therefore, permeating (glycerol, dimethyl sulfoxide) and non-permeat-http://epublishing.ekt.gr | e-Publisher: EKT |
... In recent decades, the use of soy lecithin has been demonstrated to be safer than egg yolk in terms of biosecurity (Bousseau et al., 1998), and it has been used for sperm cryopreservation in species such as eel (Tanaka et al., 2002), bull (Aires et al., 2003), stallion (Aurich et al., 2007), boar (Zhang et al., 2009), human (Reed et al., 2009), and particularly, ram (Gil et al., 2003;de Paz et al., 2010;Forouzanfar et al., 2010). Lecithin has been reported to have neither a cytotoxic effect (Fiume, 2001) nor a negative effect on sperm motility (Hong et al., 1986), Sunflower lecithin is a type of phospholipid found in sunflower seeds. It is a good source of phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol. Sunflower lecithin can replace soy bean lecithin as an alternative to egg yolk in mammalian semen extender during cryopreservation even though there has not been any report on the use of sunflower lecithin in preserving Kalahari Red goat semen. ...
Soybean lecithin had been used as an alternative to egg yolk in domestic animal semen extender during cryopreservation due to its characteristic phospholipid content which played a major cryoprotective role. This composition of soybean lecithin informed the replacement of soybean with sunflower lecithin (SL) in the extender for the Kalahari Red (KR) buck semen cryopreservation in this study. Effect of different levels of SL on the quality of the KR buck semen during cryopreservation using slow freezing method was evaluated. Semen samples were collected from four KR bucks of between two and two and half of age using artificial vagina, evaluated for motility and then diluted in extenders containing different levels of SL (1.5%, 3.0% and 4.5%) as experimental group and 0% SL or 20% egg yolk as control. Semen parameters including motility, acrosome integrity (AcI), membrane integrity (MI), malondialdehyde (MDA) concentration, cholesterol level and seminal arginase activity were evaluated for. The results showed that motility, acrosome integrity (AI) and membrane integrity were comparable at 0%, (22.00 ± 4.58, 82.00 ± 3.51 and 96.00 ± 2.03); 1.5%, (23.00 ± 2.08, 87.00 ± 3.79 and 89.00 ± 2.08); 3.0%, (13.00 ± 2.52, 81.33 ± 0.41 and 76.67 ± 1.20) and 4.5% (11.00 ± 4.51, 85.33 ± 9.88 and 84.00 ± 8.50), respectively, after thawing. SL at 0% had the highest ( P < 0.05) values for MDA, cholesterol and seminal arginase activity (1.10 ± 0.008 nmol/ml, 236.35 ± 4.08 mg/dl and 0.54 ± 3.3 E-3 units/mg protein, respectively). Our data suggest that 1.5% sunflower lecithin can be used in place of soy lecithin as a substitute for egg yolk during the cryopreservation of caprine semen.
... This variation in response to the different skin care products could be attributed to the variation in uptake of extracutaneous lipids by the epidermis, which occurs by unknown mechanisms (Feingold, 2007). The addition of C12-16 alcohols, hydrogenated lecithin, palmitic acid and commiphora mukul resin extract (Fiume, 2001;Shah et al., 2012;Park et al., 2016) to cream 2 only improved the subjective opinion of the treated individuals, who considered cream 2 as "the most pleasant". DAC (cream 3), a base cream used nationwide in German hospitals, did not improve any biophysical skin parameter in the tested groups. ...
Skin aging is associated with alterations of surface texture, sebum composition and immune response. Mechanical stress induces repair mechanisms, which may be dependent on the age and quality of the skin. The response to mechanical stress in young and aged individuals, their subjective opinion and objective effectiveness of skin care products were evaluated by biophysical skin quality parameters (stratum corneum hydration, transepidermal water loss, skin pH, pigmentation and erythema) at baseline, 1, 6, 24hours and 7days at the forearms of 2 groups of healthy volunteers, younger than 35 years (n=11) and older than 60 years (n=13). In addition, casual surface lipid composition was studied under the same conditions at the baseline and day 7 after mechanical stress induction. Evaluations were also performed in stressed skin areas treated daily with skin care products and the subjective opinion of the volunteers was documented. The tested groups exhibited age-associated baseline skin functions as well as casual surface lipid composition and different reaction patterns to mechanical stress. Skin care was more effective in normalizing skin reaction to stress in the young than in the aged group. The subjective volunteer opinion correlated with the objective measurements.
... In this study, we have determined the effect of two different pyruvate concentrations and, at the same time, whether trehalose could be a more efficient protective agent than sucrose. The use of soy lecithin (L-a-phosphatidylcholine) has been demonstrated to be safer than egg yolk in terms of biosecurity [53] and to have neither a cytotoxic effect [54] nor a negative effect on sperm motility [55]. Lecithin is a normal constituent of the sperm plasma membrane [56] and the use of lecithin-containing extenders has been useful for maintaining high quality values in refrigerated [57] and frozen-thawed [6] ram spermatozoa [13,14,[17][18][19][57][58][59][60][61]. ...
Background: One of the main drawbacks of refrigerated and frozen-thawed semen is lipid peroxidation and the subsequent generation of reactive oxygen species from cellular metabolism. In this study, we tested the hypothesis that the use of antioxidant compounds improves the frozen-thawed sperm quality. We analysed the effect of different antioxidants, or antioxidant-like additives, upon the processes involved in cooling and freeze-thawing ram semen. Methods: Sperm motility, plasma membrane integrity and stability, and mitochondrial membrane potential (MMP) were tested immediately after thawing and following incubation for 3 h and 6 h at 37°C. Results: The addition of oleic/linoleic acid did not improve sperm viability, although it resulted in increased motility after refrigeration and rewarming, similar to that found with pyruvic acid. In frozen-thawed samples, the effect of 75 mM ascorbic acid was beneficial and improved viability, membrane stability, MMP and motility. Pyruvic acid, melatonin, pinoline and N-acetyl cysteine, or the combination of certain antioxidants such as oleic/linoleic acids with tocopherol, lipoic and ascorbic acids, melatonin and pinoline, N-acetyl cysteine and GSH did not significantly improve the frozenthawed sperm quality. Thawed samples supplemented with lecithin scored higher (p<0.001) membrane integrity and stability and MMP values than controls. However, the alterations induced in the inner mitochondrial membrane resulted in a very low proportion of functional mitochondria in a time-dependent manner after thawing. These detrimental effects were prevented by seminal plasma proteins, which enhanced the protective effect of lecithin. Conclusion: Seminal plasma proteins strengthened the cryoprotective ability of lecithin and not only were sperm viability and membrane stability well maintained, but mitochondrial functionality was preserved. General significance: Lecithin together with seminal plasma proteins may be used as cryoprotectants for ram semen.
... ORG-CRO was constituted of PC 200 mM, a concent r a t i o n effe c t i ve fo r pe n et r a t i on e nh a nc e m e n t , isopropylpalmitate, a biocompatible oil particularly suitable for transdermal delivery, and water (Fiume 2001;Changez et al. 2006). In ORG-CRO the reverse micelles initially formed, upon further addition of water linearly grew and entangled, finally constituting a threedimensional network of interpenetrating worm-like micelles, stabilized by hydrogen bonds between PC and polar solvent molecules (Vintiloiu and Leroux 2008;Kumar and Katare 2005). ...
The present study describes the production and characterization of phosphatidylcholine based ethosomes and organogels, as percutaneous delivery systems for crocin. Crocin presence did not influence ethosome morphology, while the drug slightly increased ethosome mean diameter. Importantly, the poor chemical stability of crocin has been found to be long controlled by organogel. To investigate the performance of phosphatidylcholine lipid formulations as crocin delivery system, in vivo studies, based on tape stripping and skin reflectance spectrophotometry, were performed. Tape stripping results suggested a rapid initial penetration of crocin exerted by the organogel, probably due to a strong interaction between the peculiar supramolecular aggregation structure of phospholipids in the vehicle and the lipids present in the stratum corneum and a higher maintenance of crocin concentration in the case of ethosomes, possibly because of the formation of a crocin depot in the stratum corneum. Skin reflectance spectrophotometry data indicated that both vehicles promoted the penetration of crocin through the skin, with a more rapid anti-inflammatory effect exploited by ethosomes, attributed to an ethanol pronounced penetration enhancer effect and to the carrier system as a whole.
... In fact, the other lipidic nanocarriers contain saturated lipids in their structure, which limit the application of them in food. Lecithin, as used in the synthesis of liposomes and phytosomes, is a natural compound commonly used in several applications, including food products, such as mayonnaise, and in these uses they are generally regarded as safe (GRAS) recommended by the food and drug administration (FDA) (Lecithin, 2001). There are sufficient reasons indicating that the phytosome is superior to the liposomes in structural integrity as discussed previously in this study. ...
Flavonoids have many nutritional-therapeutic and preservative features. Therefore, the aim of using them for fortifying food products could provide new horizon in developing new functional foods. However, there are several problems associated with the use of these phyto-active constituents in foods and food beverages. Nano-phytosome is one of the newest lipid based nano-carrier and fast growing attractive way of delivering botanical based nutraceuticals. Although the nano-phytosome technology has been developed for pharmaceutical applications, it could be potentially used in food products for designing novel functional foods and beverages. The current review represents physicochemical properties and potential applications of nano-phytosome as a carrier of food bioactive compounds in development of functional foods.
... In recent decades, the use of soy lecithin has been demonstrated to be safer than egg yolk in terms of biosecurity (Bousseau et al, 1998), and it has been used for sperm cryopreservation in species such as eel (Tanaka et al, 2002), bull (Aires et al, 2003), stallion (Aurich et al, 2007), boar (Zhang et al, 2009), human (Reed et al, 2009), and particularly, ram de Paz et al, 2010;Forouzanfar et al, 2010). Lecithin has been reported to have neither a cytotoxic effect (Fiume, 2001) nor a negative effect on sperm motility (Hong et al, 1986), whereas lysophosphatidylcholine and other fatty acids have inhibitory effects on sperm motility and induce acrosomal damage. ...
... Pre-study screen, eligibility and selection 29 12.3 Allocation to entry number and study treatment 30 12.4 Assessments 30 12.5 Compliance 31 12. 6 Adverse Events (AEs) 31 12.7 Serious Adverse Events (SAEs) 31 12.8 Safety 31 12.9 Post-study screen 32 12. 10 Criteria for withdrawal or premature discontinuation 32 23 -Healthy males as assessed by the health and lifestyle questionnaire, physical examination and results of the pre-study laboratory tests -Age at day 01 of the study: 50-80 years -Body Mass Index (BMI) 33 kg/m 2 -Normal Dutch eating habits, including use of breakfast -Willing not to use supplements containing B-vitamins, lecithin, choline (derivatives) or betaine from the oral information session until the end of the study -Voluntary participation -Having given their written informed consent -Willing to comply with the study procedures, including dietary restrictions -Willing to accept use of all nameless data, including publication, and the confidential use and storage of all data -Willing to accept the disclosure of the financial benefit of participation in the study to the authorities concerned -Exclusion criteria: ...
Protocol for Study 4
(840 KB PDF).
... They attribute the effectiveness of these L/T blends as oil-in-water emulsifiers both to the complementary shapes of Tween 80 (hydrophilic) and lecithin (hydrophobic), which enable a densely-packed surfactant monolayer to form at the oilwater interface (see Fig. 1), and to the steric hindrance of oil droplet coalescence by Tween 80's large polyoxyethylene chains. Since lecithin and Tween 80 are nontoxic surfactants (Carlsson et al., 2006;Fiume, 2001), the prospect of an oil dispersant based on lecithin-Tween 80 blends warrants further study (Nyankson et al., 2015). ...
Effectiveness of oil spill dispersants containing lecithin/Tween 80 (L/T) blends in ethanol was measured as a function of L:T ratio, surfactant:solvent ratio, solvent composition, and dispersant:oil ratio (DOR) using baffled flask dispersion effectiveness tests. Optimal L:T ratios are between 60:40 and 80:20 (w/w); at higher L:T ratios, effectiveness is limited by high interfacial tension, while at lower L:T ratios, insufficient lecithin is present to form a well-packed monolayer at an oil-water interface. These optimal L:T ratios retain high effectiveness at low DOR: 80:20 (w/w) L:T dispersant is 89% effective at 1:25 DOR (v/v) and 77% effective at 1:100 DOR (v/v). Increasing surfactant:solvent ratio increases dispersant effectiveness even when DOR is proportionally reduced to keep total surfactant concentration dosed into the oil constant. Replacing some of the ethanol with octane or octanol also increases dispersant effectiveness, suggesting that ethanol's hydrophilicity lowers dispersant-oil miscibility, and that more hydrophobic solvents would increase effectiveness.
... Nanoemulsions containing a synthetic chalcone for cl treatment optimization study, since they are widely used in the preparation of nanostructured systems due to their low toxicity. [27][28][29] In addition, lecithin has high affinity for cell membranes, affording increased drug absorption, which is ideal for the development of nanoemulsions. Co-surfactants can be employed to stabilize the interface by steric hindrance, thereby forming more stable emulsions. ...
Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2² full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g⁻¹) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.
... Phospholipids are biocompatible materials with verified safety profile [82]. The greatest contribution to drug delivery is their ability to form (upon hydration) supramolecular self-assembled structures, e.g. ...
Drug delivery to or via the skin presents both unique opportunities and obstacles due to skin structure, physiology, and barrier properties. The skin, the largest organ of the body, may be viewed either as a natural protective barrier against penetration of toxic exogenous compounds, excessive loss of water and other essential compounds, or as a promising portal of entry for drugs for local and/or systemic action. Many novel lipid nanocarriers have been designed for topical application of drugs since they allow these molecules to overcome the skin barrier and improve cutaneous bioavailability. The increased drug absorption is often a consequence of a reversibly disrupted barrier function of the skin by the vehicle itself or by specific ingredients figuring in the topical formulation that act as penetration enhancer. Micro/nanoemulsions and lipid nanoparticles are known to provide several advantages over conventional formulations in terms of stability and skin penetration enhancement. However, their characteristics in the original form are low viscous liquids and colloidal dispersions. Therefore, their topical application may be limited in some cases. This review describes recent works in formulating lipid nanocarriers, especially in the semi-solids and hydrogels forms, and reports their special features for biomedical and dermocosmetic applications.
... The physiological impact is the enhancement of the skin barrier function and the stabilising effect of the natural transepidermal water loss [40]. Lecithins usually are non-irritating and non-sensitizing for animal and human skin [41]. Moreover lecithin compounds present an affinity to cellular membranes thus leading to an increased absorption of several drugs [31]. ...
... Lecithin has been isolated from egg yolk, due to the chemical composition, is more valuable than the lecithin of plant origin, since the composition contains up to 80 % choline. It is known that choline is a main source of a precursor of the neurotransmitter-acetylcholine (Fiume 2001). Choline plays a role in liver function, prevention of cancer, and ensures the proper functioning of brain and development of memory (maintenance of learning memory performance) (Zeisel 1992;Zeisel 2000). ...
Phospholipids are one of the classes of lipids, which are a major component of all cell membranes. Phosphatidylcholine (PC) is the main phospholipid present in egg yolk. The phospholipids extract from enriched egg yolk was separated using the two-dimensional high performance liquid chromatography in off-line system coupled with electrospray ionization tandem mass spectrometry (off-line HPLC-ESI-MS/MS). In the first dimension, a preparative C18 column was used, and on the second dimension, a separation was performed on N,O-dialkylphosphoramidate bonded silica column. In the analyzed egg yolk, 15 different phosphatidylcholines was found. From among the identified fatty acid of PC, a large part constitutes docosahexaenoic acid (ω-3, 22:6, DHA) and linoleic acid (ω-6, 18:2, LA).
... It has also been shown that lipid vesicles can improve local delivery and sustained release of topical drugs [131--137]. Furthermore, vesicles made of phospholipids have high biocompatibility and are therefore considered relatively safe to use [138]. ...
Background:
Chronic wounds often contain high levels of proinflammatory cytokines that prolong the wound-healing process. Patients suffering from these conditions are likely to benefit from topical rifampicin therapy. Although recent research indicates considerable anti-inflammatory properties of the antibiotic, currently, there are no commercial topical wound healing products available. To address this medical need, a liposomal drug delivery system was developed. A mechanistic investigation outlined major influences of wound environments that affect the release kinetics and, as a consequence, local bioavailability.
Methods:
Liposomes were prepared using the thin-film hydration method and subsequently freeze-dried at the pilot scale to improve their stability. We investigated the influence of oxidation, plasma proteins, and lipolysis on the in vitro release of rifampicin and its two main degradation products using the Dispersion Releaser technology. A novel simulated wound fluid provided a standardized environment to study critical influences on the release. It reflects the pathophysiological environment regarding pH, buffer capacity, and protein content.
Results:
During storage, the liposomes efficiently protect rifampicin from degradation. After the dispersion of the vesicles in simulated wound fluid, despite the significant albumin binding (>70%), proteins have no considerable effect on the release. Also, the presence of lipase at pathophysiologically elevated concentrations did not trigger the liberation of rifampicin. Surprisingly, the oxidative environment of the wound bed represents the strongest accelerating influence and triggers the release.
Conclusion:
A stable topical delivery system of rifampicin has been developed. Once the formulation comes in contact with simulated wound fluid, drug oxidation accelerates the release. The influence of lipases that are assumed to trigger the liberation from liposomes depends on the drug-to-lipid ratio. Considering that inflamed tissues exhibit elevated levels of oxidative stress, the trigger mechanism identified for rifampicin contributes to targeted drug delivery.
Foam formulations are safe and effective therapy options for the treatment of chronic skin conditions that require the application of a topical formulation to delicate skin areas, such as scalp psoriasis or seborrheic dermatitis. This study focused on the development of foamable emulsions based on aqueous phospholipid blends. The effects of cosurfactants (nonionic Lauryglucoside (LG); zwitterionic Lauramidopropyl betaine (LAPB)), as well as of oil phases of different polarities, namely paraffin oil (PO), medium-chain triglycerides (MCT) and castor oil (CO), were investigated. The foaming experiments showed that both the type of cosurfactant, as well as the type of oil phase, affects the quality of the resulting foam. Emulsions that were based on a combination of hydrogenated lysophosphatidylcholine (hLPC) and a non-hydrogenated phospholipid, as well as LG as a cosurfactant and MCT as an oil phase, yielded the most satisfactory results. Furthermore, profile analysis tensiometry (PAT), polarization microscopy and laser diffraction analysis were used to characterize the developed formulations. These experiments suggest that the employed phospholipids predominantly stabilize the emulsions, while the cosurfactants are mainly responsible for the formation and stabilization of the foams. However, it appears that both sets of excipients are needed in order to acquire stable emulsions with satisfactory foaming properties.
Basic substances are a group of substances that have recently been regulated to give legislative coverage to common products such as vinegar, beer, milk and sugar, traditionally used by farmers for crop protection, and which may also include foodstuffs. They are regulated by article 23 of Regulation (EC) N. 1107/2009 concerning the placing of plant protection products on the market. According to this article, basic substances are not predominantly used as plant protection products but may be of value for plant protection. They do not have an immediate or delayed harmful effect on human or animal health nor an unacceptable effect on the environment. This review analyses the process for approval for basic substances under current European rules. Furthermore, every approved basic substance in the EU, at the time of writing, is described in detail in relation to its activity in plant protection. Considering that the use of basic substances is particularly important for organic farming, basic substances authorized in organic production under current organic legislation and under the new Regulation (EU) 2018/848 on organic production that will apply from 1 January 2022 repealing Council Regulation (EC) N. 834/2007 are reported. Finally, the review highlights the positive aspects and critical issues of basic substances.
The role of cosmetic products is rapidly evolving in our society, with their use increasingly seen as an essential contribution to personal wellness. This suggests the necessity of a detailed elucidation of the use of nanoparticles (NPs) in cosmetics. The aim of the present work is to offer a critical and comprehensive review discussing the impact of exploiting nanomaterials in advanced cosmetic formulations, emphasizing the beneficial effects of their extensive use in next-generation products despite a persisting prejudice around the application of nanotechnology in cosmetics. The discussion here includes an interpretation of the data underlying generic information reported on the product labels of formulations already available in the marketplace, information that often lacks details identifying specific components of the product, especially when nanomaterials are employed. The emphasis of this review is mainly focused on skincare because it is believed to be the cosmetics market sector in which the impact of nanotechnology is being seen most significantly. To date, nanotechnology has been demonstrated to improve the performance of cosmetics in a number of different ways: 1) increasing both the entrapment efficiency and dermal penetration of the active ingredient, 2) controlling drug release, 3) enhancing physical stability, 4) improving moisturizing power, and 5) providing better UV protection. Specific attention is paid to the effect of nanoparticles contained in semisolid formulations on skin penetration issues. In light of the emerging concerns about nanoparticle toxicity, an entire section has been devoted to listing detailed examples of nanocosmetic products for which safety has been investigated.
Phospholipids
are attractive components in cosmetic products because of their natural origin and multifunctional properties. They are used, technically as surface-active compounds, but also as cosmetic actives and modulator of skin penetration. Three classes of phospholipids are being used in cosmetics: saturated and unsaturated phospholipids and monoacylphospholipids (lyso-phospholipids). Whereas the use of monoacylphospholipids is limited to technical use as emulsifiers, the cosmetic use of saturated and unsaturated phospholipids is much broader. The latter are used as actives; additionally saturated phospholipids are used as surface-active compounds, whereas unsaturated phospholipids are suitable to enhance skin penetration. The relation of phospholipids to nanotechnology is apparent when they are, e.g., used as an emulsifier in “nano-emulsions” and as component of “nano-liposomes”, having particle sizes in the nano-range. Regulatory authorities discriminate, however, between nanoparticles comprising solid inorganic non-biodegradable particles, with potential (systemic) toxicity, and flexible lipid biodegradable carriers, respectively, comprising, e.g., phospholipids which are non-toxic [1] and fall apart in the skin. Since basically the particle characteristics in the formulation and the component of the particles are believed to cause the desired beneficial cosmetic skin effects, in this chapter the use and degree of skin interaction of especially natural phospholipids as cosmetics ingredient in traditional and nano-cosmetic carriers are described and demonstrated by means of illustrative products.
KeywordsPhospholipidsLiposomesEmulsionsLamellar structuresSolubilizersBiocompatibility
Nature offers a tremendous potential in medicine field. Natural antioxidant molecules inhibit or quench free radical reactions and delay or inhibit cellular damage. In the last few years researchers have been focusing on the health benefits of natural products. Particularly some dietary nutrients, such as curcumin, crocin, resveratrol, quercetin, coenzyme Q10, vitamin C, as well as some polysaccharides have been evaluated for their numerous and unique therapeutic properties. This review focuses on examples of pharmaceutical applications of natural anti-oxidants, with special regards to their encapsulation in micro- and nano- delivery systems. In vitro and in vivo studies have been conducted to investigate the physicochemical and pharmacological properties of different delivery systems containing antioxidant molecules. For instance, ethosomes, organogels, monoolein aqueous dispersions and solid lipid nanoparticle have been considered. It was found that micro and nanoencapsulation strategy can improve the solubility of lipophilic molecules and the chemical stability of labile antioxidants, thus prolonging their efficacy. In vitro and in vivo studies have highlighted that antioxidant encapsulation prolongs release kinetics, bioavailability and antioxidant effects. Noticeably, some encapsulated antioxidants effectively inhibit cancer cell proliferation, cell migration and colony formation, thus suppressing cancer progression.
Structured phosphatidylcholine was successfully produced by acidolysis between phosphatidylcholine and free medium chain fatty acid, using phospholipase A1 immobilized on Duolite A568. Response surface methodology was applied to optimize the reaction system using three process parameters: molar ratio of substrates (phosphatidylcholine to free medium chain fatty acid), enzyme loading, and reaction temperature. All parameters evaluated showed linear and quadratic significant effects on the production of modified phosphatidylcholine; molar ratio of substrates contributed positively, but temperature influenced negatively. Increased enzyme loading also led to increased production of modified phosphatidylcholine but only during the first 9 hours of the acidolysis reaction. Optimal conditions obtained from the model were a ratio of phosphatidylcholine to free medium chain fatty acid of 1:15, an enzyme loading of 12%, and a temperature of 45℃. Under these conditions a production of modified phosphatidylcholine of 52.98 % were obtained after 24 h of reaction. The prediction was confirmed from the verification experiments; the production of modified phosphatidylcholine was 53.02%, the total yield of phosphatidylcholine 64.28% and the molar incorporation of medium chain fatty acid was 42.31%. The acidolysis reaction was scaled-up in a batch reactor with a similar production of modified phosphatidylcholine, total yield of phosphatidylcholine and molar incorporation of medium chain fatty acid. Purification by column chromatography of the structured phosphatidylcholine yielded 62.53% of phosphatidylcholine enriched with 42.52% of medium chain fatty acid.
The rapid advance in the field of nanotechnology especially in nanopharmaceutics have led to the development of a discipline called nanotoxicology. Various European, US (ISO, OECD, etc.), and Japanese regulatory agencies have some guidelines in the field of pharmaceutical toxicology, but there is an emergency need for the guidelines revision in the field of nanotoxicology due to size influence. It is interesting to note that there are efficient standard analyses for chemical and pharmaceutical drugs in the field of genotoxicity. However, some of them will not be efficient in nanotoxicology such as Ames (OECD 471), although in other toxicology analyses, it seems that just more attention in some pathways is enough. For example, in hemocompatibility tests with more emphasis in the complement system. Overall, although the nanopharmaceutical drugs have attracted high impact in the cancer or other therapies but attention to the eventually hidden side effects derived from them is necessary.
The present opinion deals with the re-evaluation of lecithins (E 322) when used as a food additive. Lecithins (E 322) is an authorised food additive in the EU according to Annex II and Annex III to Regulation (EC) No 1333/2008 on food additives, and have been previously evaluated by JECFA in 1973 and by the SCF in 1982. Among lecithins, phosphatidylcholine is hydrolysed in choline in the cytidine-5-diphosphate-choline pathway in all cells of the body. Following the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010, the Panel concluded that there was no need for a numerical ADI for lecithins (E 322) and that there was no safety concern for the general population from more than 1 year of age at the refined exposure assessment for the reported uses of lecithins (E 322) as a food additive. The Panel further concluded that there is no safety concern for the exposure to the choline from lecithins (E 322) as a food additive at use and use levels reported by industry. For infants (from 12 weeks up to 11 months of age), the Panel concluded that there was no safety concern at the refined exposure assessment for the reported uses of lecithins (E 322) as a food additive and for the choline from lecithins (E 322) as a food additive at use and use levels reported by industry. For infants and young children consuming foods for special medical purposes, the Panel concluded that there was no safety concern with respect to the refined exposure assessment for the reported uses of lecithins (E 322) as a food additive and for exposure to choline resulting from these uses of lecithins (E 322).
Lecithin is a phosphatide found in all living organisms, both plants and animals. It is composed of a complex mixture of acetone-insoluble phosphatidyl esters, which consists mainly of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl inositol combined with other substances such as triglycerides, fatty acids, and carbohydrates. Lecithin is an emulsifying agent and has been tried in the treatment of dementia as a source of choline.
OBJECTIVE: To determine lysolecithin and in vitro hemolysis of propofol nano-injection. METHODS: An HPLC method was established for determination of lysolecithin. The sample was analyzed with a Platisil C18 column (4.6 mm × 250 mm, 5 μm) at 30°C. Mobil phase A was acetonitrile-water (9:1). Mobil phase B was 0.2% phosphoric acid aqueous solution (pH adjusted to 2.5 with triethylamine). Gradient elution program was used as follows; 0 min, 60% A; 15 min, 60% A; 16 min, 90% A; 22 min, 90% A; 23 min, 60% A; 35 min, 60% A. The flow rate was 1.2 mL ·min-1. The detection wave length was set at 210 nm. Spectrophotometric method was used to determine hemolysis. RESULTS: The linear range of the calibration curve for lysolecithin was 19. 8-198.0 μg · mL-1 (r=0.9998). The average recovery was 102.0% and RSD was 0.63% (n=9). The lysolecithin contents of three batches of samples were 0.313, 0.273 and 0.318 mg · mL-1, respectively. The hemolysis rates were 2.70%, 3.37% and 3.04%, respectively. CONCLUSION: The HPLC method can be used for the determination of lysolecithin in propofol nano-injection. The hemolysis rates of three batches of samples were less than 5%.
Nanotechnology is the key technology of the 21st century. The possibility to exploit the structures and processes of high-molecular-weight biomolecules like proteins, nucleic acids and synthetic polymers (silicon, polymethylacrylate, etc.) for novel functional materials, biosensors, biomicroelectromechanical systems (bioMEMS) and smart drug delivery systems has created the rapidly growing field of "bionanotechnology". In this chapter, the current state of the art and availability of nanotechnologies in medical and pharmaceutical sciences is reviewed. Drug and gene delivery, tissue engineering, biosensors, and safety aspects will be discussed as the main fields to show the potential applications, as well as limitations, of the techniques. The main focus is on the fabrication, miniaturization and pharmaceutical use of smart drug delivery systems like microneedles, bioMEMS and biosensing microchips. In addition, the safety aspects and biohazards of nanosystems are also discussed.
Ferulic acid (4-hydroxy-3-methoxycinnamic acid), an effective component of medical plant, is a phenolic acid with low toxicity that can be absorbed and easily metabolized in the human body. The solubility of Ferulic Acid (FA) is very low in aqueous solutions which can cause problem in preparation of pharmaceutical products, but it can easily be dissolved in oil/water interface of nano-emulsions. In the present work, a kind of ferulic acid nano-emulsion was prepared using the spontaneous emulsification method which occurs when an organic phase and an aqueous phase are mixed. A chemometrics approach has been used to optimize the size of FA nanoemulsions.The experiments were performed according to a Box-behenken experimental design, one of the most suitable experimental design for modeling studies. The effect of three experimental parameters on droplet size was studied using multivariate analysis. The factors studied and the related levels were the concentration of lecithin (0.7-2 % w/w, in aqueous phase), the concentration of tween-80 (2-8 % w/w, in aqueous phase) and sounication time (10-45 minutes). In all the experiments, the water phase was added to the organic phase including lecithin, tween-80 and FA in ethanol solvent. Then experimental droplet sizes were fitted to the polynomial model. Good descriptive and predictive ability of the model was verified as high values of the statistics R2 (0.996) and F (112.5) were obtained for the linear relationship between predicted and experimental values of the dependent variable.
This study was conducted to investigate whether soy lecithin can be used as an alternative cryoprotectant to establish a procedure that does not require the use of egg yolk to cryopreserve rabbit strains. Semen from Japanese White rabbits was frozen with HEPES extender containing 20% egg yolk (EYH), 0.5% (Lec-0.5), 1.5% (Lec-1.5), 2.5% (Lec-2.5), or 3.5% (Lec-3.5; wt/vol) lecithin (type IV-S, ≥30%), and the motility of thawed sperm was analyzed. The sperm motility in the Lec-1.5 group was significantly higher than that in the Lec-2.5 and 3.5 groups and equivalent to the EYH group. From 17 rounds of artificial insemination with frozen-thawed sperm in the EYH and Lec-1.5 groups, 12 rabbits in both groups were pregnant (70.6%) and delivered offspring. The litter size was 3.3 in the EYH group and 5.1 in the Lec-1.5 group. These results indicate that soy lecithin can be used as a substitute for egg yolk as a cryoprotectant on the basis of motility and fertility of the frozen-thawed rabbit sperm and that 1.5% lecithin (type IV-S, ≥30%) in the semen extender was the optimum concentration for rabbit sperm cryopreservation.
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Abstract The purpose of this study was to develop a water/oil microemulsion containing lidocaine hydrochloride (4%) and to compare its local anaesthetic efficacy with commercial products. A pseudoternary diagram (Km:1/1 or 1/2) was constructed using lecithin/ethanol/oil/water. The droplet size, viscosity and release of the microemulsions were evaluated. Tail flick tests were conducted for in vivo effectiveness; the initiation time of effect, maximum effect, time to reach maximum effect, and relative efficacy were evaluated. The drug caused a significant increase in droplet size. The use of olive oil resulted in a decrease in the solubilisation parameter, as well as a reduction in the release. The droplet size and viscosity of the microemulsion composed of Miglyol/lecithin/ethanol/water/drug (Km:1/2) was lower than other microemulsions (8.38 nm, 6.9 mPa), and its release rate (1.61 mg/h) was higher. This system had a faster and more efficient anaesthetic effect than the other microemulsions and commercial products. Results indicate that a water/oil type microemulsion (Miglyol/lecithin/ethanol/water) has promising potential to increase the local anaesthetic effect.
Phosphatidylcholine (PC), phosphatidylethanolamine (PE), ethanolamine plasmalogen (EPLAS), sphingomyelin (SPH), phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin (CL), phosphatidylglycerol (PG) and phosphatidic acid (PA) were dispersed together in Cs(ethylenedinitrilo)tetraacetic acid-scrubbed chloroform/methanol solution, and high resolution 31P nuclear magnetic resonance spectra were recorded. In separate titration experiments, Mg2+ and Ca2+ were added to the dispersed phospholipid mixture to determine the relative interaction potentials of each of the phospholipids for each of the added cations. The association of cations with individual phospholipids was indicated by 31P chemical-shift changes, signal broadening, signal quenching or a combination of these. The titrations revealed that CL had the highest, and PA the next highest, interaction potential for Mg2+ cations. In contrast, PS and PA had the highest, and CL the next highest, interaction potential for Ca2+. Considering only interactions with Ca2+ ions, the phospholipids can be divided into three distinct groups: PS and PA (high interaction potential); CL, PI and PG (intermediate interaction potential); and EPLAS, PE, SPH and PC (essentially no interaction potential). The two phospholipids with the least interaction potential for either of the alkaline-earth cations were PC and SPH. Na+ and K+ ion interactions with PA, CL, PI and PG were unique and resulted in positive chemical-shift changes relative to the chemical shifts in the presence of Cs+ ions. Relative to both Cs+ and K+ ions, chemical shifts in the presence of Na+ ions were deshielded delta greater than 0.1 ppm in the order PA greater than CL greater than PI greater than PG.
Phospholipids of 16 malignant and 11 non-malignant human colon specimens were analyzed using a chloroform-methanol analytical reagent in conjunction with 31P magnetic resonance spectroscopy (MRS) at 202.4 MHz. Sixteen individual generic phospholipids were identified and quantified for statistical intergroup comparisons. Statistically significant elevations in the relative concentrations of lysophosphatidylcholine and phosphatidylcholine plasmalogen were seen in malignant tissues along with significantly depressed levels of sphingomyelin and phosphatidylethanolamine plasmalogen. The malignant and non-malignant tissue groups were further differentiated by the detection of the minor phospholipids, lysophosphatidylcholine plasmalogen, lysophosphatidylethanolamine plasmalogen, lysophosphatidic acid and phosphatidylglycerol exclusively present in the malignant tissues and by significant changes in computed phospholipid metabolic indices that were dominated by choline containing lipids. The 31P MRS methods used represent an advancement over previous protocols for identifying and quantifying major and minor tissue phospholipids making this the first direct study of membrane phospholipids in human colon tissues using 31P MRS. The phospholipid profiles obtained may provide important information regarding the nature of the malignant cell's membrane system and identify markers which may be used to estimate malignant propensity, aggressiveness of disease and provide prognostic information.
A high-performance liquid chromatographic method for the quantification of major phospholipid classes is described. The separation was performed on Ultrasphere SI silica gel columns with a mobile phase of acetonitrile-methanol-85% phosphoric acid (100:10:1.8. v/v) using isocratic elution and UV detection at 203 nm. Complete separation of phosphatidylserine, phosphatidylethanolamine, plasmalogen, phosphatidylcholine and sphingomyelin was achieved within 8 min. The plasmalogen was resolved from phosphatidylethanolamine in hydrochloric acid-derivatized samples, or without derivatization using a mobile phase composition of 100:40:0.4. The phospholipids were quantified by peak-area integration by means of the calibration. The detection limit is 5 ng. Human erythrocyte ghost membranes, lymphocytes and thrombocytes were analysed for these phospholipids. This method is suitable for routine clinical studies of membrane disorders in health, toxicity and disease, as well as in research.
The major route of phosphatidylcholine (Ptd-choline) biosynthesis in mammalian cells is the CDP-choline pathway which involves stepwise conversion of choline to phosphocholine (P-choline), cytidine diphosphate choline (CDP-choline), and Ptd-choline. Our previous studies with electropermeabilized (EP) rat glioma (C6) cells have indicated that the intermediates of this pathway are not freely diffusible in the cell but are channeled toward synthesis of Ptd-choline (George, T.P., Morash, S.C., Cook, H.W., Byers, D.M., Palmer, F. B. St.C., and Spence, M.W. (1989) Biochim. Biophys. Acta 1004, 283-291). In this study, Ca(2+)-[ethylene-bis(oxyethylenenitrilo)]tetraacetic acid buffers were used to investigate the role of intracellular free Ca2+ levels in functional organization of this pathway in EP glioma cells. In EP cells reduction of free Ca2+ in the medium from 1.8 mM to less than 200 nM resulted in 2-3-fold stimulation of exogenous [3H]choline and [14C]P-choline incorporation into Ptd-choline whereas incorporation of exogenous CDP-[14C]choline was augmented 100-fold; there was no uptake or incorporation of labeled P-choline or CDP-choline in intact cells. In EP cells incubated at 1.8 mM Ca2+ the water-soluble products of choline metabolism (choline, P-choline, CDP-choline, and glycerophosphocholine) were retained at 37 degrees C; in contrast, in the presence of 100 nM Ca2+ there was uniform leakage of these metabolites. Experiments with hemicholinium-3, an inhibitor of choline transport, and EP cells at 100 nM Ca2+ show that linkage of choline transport and Ptd-choline biosynthesis is also dependent on Ca2+. These results suggest that channeling of intermediates in the CDP-choline pathway of Ptd-choline biosynthesis in glioma cells is mediated by intracellular Ca2+ levels that may coordinately regulate the steps involved in conversion of choline to Ptd-choline.
The effect of a number of growth factors on phosphatidylcholine (PtdCho) turnover in Swiss-3T3 cells was studied. Phorbol 12-myristate 13-acetate (PMA), bombesin, platelet-derived growth factor (PDGF) and vasopressin rapidly stimulated PtdCho hydrolysis, diacylglycerol (DAG) production, and PtdCho synthesis. Insulin and prostaglandin F2 alpha (PGF2 alpha) stimulated PtdCho synthesis, but not its breakdown, whereas epidermal growth factor (EGF) and bradykinin were without effect. Stimulation of PtdCho hydrolysis by the above ligands resulted in increased production of phosphocholine and DAG (due to phospholipase C activity) and significant amounts of choline, suggesting activation of a phospholipase D as well. CDP-choline and glycerophosphocholine levels were unchanged. Down-regulation of protein kinase C with PMA (400 nM, 40 h) abolished the stimulation of PtdCho hydrolysis and PtdCho synthesis by PMA, bombesin, PDGF and vasopressin, but not the stimulation of PtdCho synthesis by insulin and PGF2 alpha. PtdCho hydrolysis therefore occurs predominantly by activation of protein kinase C (either by PMA or PtdIns hydrolysis) leading to elevation of DAG levels derived from non-PtdIns(4,5)P2 sources. PtdCho synthesis occurs by both a protein kinase C-dependent pathway (stimulated by PMA, PDGF, bombesin and vasopressin) and a protein kinase C-independent pathway (stimulated by insulin and PGF2 alpha). DAG production from PtdCho hydrolysis is not the primary signal to activate protein kinase C, but may contribute to long-term activation of this kinase.
The in vivo biosynthesis of lecithin in rats has been studied with the precursors choline-1,2-¹⁴C, ethanolamine-1,2-¹⁴C and methionine-CH3¹⁴C or -CH3-³H. Lecithin synthesis from choline is rapid in all organs. No sex difference was observed in this pathway. The biosynthesis of lecithin by methylation of phosphatidyl ethanolamine is of quantitative significance in the liver, but not in extrahepatic tissues. More lecithin is synthesized by this pathway in female rats. In liver the lecithin synthesized via both pathways enters a common pool which is in rapid equilibrium with lecithin of blood plasma. A sex difference in the utilization of radioactive ethanolamine for the formation of phosphatidyl ethanolamine was observed (greater utilization in the female). Incorporation of ethanolamine into phospholipids of extrahepatic tissues was slow in both sexes. With labeled methionine as precursor the liver cytidine diphosphate (CDP) choline had a specific activity identical with that of liver lecithin after 20 min, while the specific activity of phosphoryl choline remained low. With labeled choline as precursor the phosphoryl choline reached a specific activity 50 times that of lecithin after 20 min, while the specific activity of CDP choline was only four times that of lecithin. These findings indicate that the reaction:
CDP choline + diglyceride ⇌ phosphatidyl choline + CMP
is freely reversible in vivo.
Incorporation of dietary phospholipids into lymph chylomicrons was studied in rats fed corn oil containing either radioactive lecithin or lysolecithin. The specific activity of lecithin-³²P in chylomicrons relative to that in the oil increased directly with the amount of lecithin fed, whereas the lecithin content of chylomicrons was constant. About 40% of the phospholipid in chylomicrons was derived from the meal when the lecithin content of the meal was 6 to 11%. When 1-palmitoyl-9,10-³H-lecithin-³²P was fed, one-fifth of the ³H recovered in chylomicrons was present in lecithin and the ratio of ³H:³²P in lecithin in chylomicrons was the same as that in the oil. When 1-palmitoyl-9,10-³H, 2-linoleoyl-1-¹⁴C-lecithin-³²P was fed, 5% of the ¹⁴C recovered in chylomicrons was found in lecithin, and the ratios of ¹⁴C:³H and of ¹⁴C:³²P in chylomicron lecithin were only 20% of that in the lecithin fed. The ratio of choline-³H to ³²P in lecithin of chylomicrons collected from rats fed choline-(methyl)-³H lecithin-³²P was the same as that in the oil meal. Up to 40% of 1-acyl lysolecithin-³²P fed with corn oil was recovered in chylomicron lecithin in 6 hours. The findings indicate that dietary lecithin is hydrolyzed and absorbed as lysolecithin and subsequently reacylated before being incorporated into lymph chylomicrons.
We have developed an improved thin-layer chromatographic method for separation of lung phospholipids. Individual phospholipids are completely separated in the first dimension. All phospholipids, except phosphatidylcholine, are then removed. The phosphatidylcholine-containing area is reacted with osmium tetroxide and saturated phosphatidylcholine species are separated from the unsaturated oxidation products by subsequent chromatography in the second dimension. This method should prove useful in studies on lung surfactant metabolism and secretion, in prediction of fetal lung maturity by analysis of amniotic fluid phospholipids, and in studies on surfactant obtained by bronchoscopy in adult lung diseases.
The skin performs a significant protective role in the human body. The epidermis is the primary and most effective barrier to the percutaneous absorption of chemicals. This function depends on the protective horny layer, the stratum corneum [5]. The epidermis produces special compounds, such as lipids, amino acids and salts, to build the membrane in the lower stratum corneum. These compounds, released by lysis of epidermal cells and organelles, constitute the barrier function of the stratum corneum conjunc-tum [6].
The book provides, in a single source, hazard-analysis information for nearly 13,000 common industrial and laboratory materials. New sections have been added to this edition to refiect the increased interest in pollution and health hazards. For public, academic and special libraries. -- AATA
One of the major drawbacks in transdermal drug delivery is the slow penetration rate of drugs through the skin. Several methods are being used to increase the penetration rate of substances through the skin, e.g., the use of penetration enhancers [9], electric forces [9], polymer devices and colloidal carriers, such as liposomes [24] and other types of vesicles [11].
Phosphatidylcholine is apparently essential for mammalian life, since there are no known inherited diseases in the biosynthesis of this lipid. One of its critical roles appears to be in the structure of the eucaryotic membranes. Why phosphatidylcholine is required and why other phospholipids will not substitute are unknown. The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. Choline kinase, the initial enzyme in the sequence, has been purified to homogeneity from kidney and liver and also catalyzes the phosphorylation of ethanolamine. Most evidence suggests that the next enzyme in the pathway, CTP:phosphocholine cytidylyltransferase, catalyzes the rate-limiting and regulated step in phosphatidylcholine biosynthesis. This enzyme has also been completely purified from liver. Cytidylyltransferase appears to exist in the cytosol as an inactive reservoir of enzyme and as a membrane-bound form (largely associated with the endoplasmic reticulum), which is activated b...
Soy lecithins are important emulsifiers used in the food, feed, pharmaceutical, and technical industries. Native lecithin
is derived from soybean oil in four steps: hydration of phosphatides, separation of the sludge, drying, and cooling. Such
lecithin has both W/O and O/W emulsifying properties. Products with improved emulsifying properties can be obtained by modifications,
involving mainly fractionation in alcohol, hydrolysis (enzymatic, acid, or alkali), acetylation, or hydroxylation. Careful
processing is required to produce lecithins of a high chemical, physical, and bacteriological quality.
Immunological and respiratory findings were studied in a group of 19 male soybean workers. Twenty control workers also participated in the immunological studies. All soybean workers had positive immediate skin reactions to soybean extract, as did 19/20 control workers. Similarly, 18/19 soy workers reacted to soy antigen prepared after separation from oil, but only 3/19 to soy lecithin antigen and 1 to soy oil antigen. A majority of soy workers (13/19) reacted to house dust. Only 3/19 soy workers had increased levels of soy-specific IgE. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers, being significantly different for dyspnea (P < 0.01).="" workers="" with="" increased="" specific="" serum="" ige="" or="" positive="" skin="" tests="" to="" house="" dust="" did="" not="" have="" any="" more="" symptoms="" than="" workers="" with="" negative="" tests.="" ventilatory="" function="" was="" significantly="" worse="" in="" soybean="" workers="" than="" expected.="" nevertheless,="" workers="" with="" positive="" skin="" or="" serological="" tests="" to="" house="" dust="" had="" across-shift="" changes="" similar="" to="" those="" with="" negative="" tests.="" these="" data="" suggest="" that="" skin="" and="" airway="" responses="" to="" soybean="" components="" (particularly="" the="" non-lipid="" ones)="" are="" very="" frequent="" among="" soybean="" workers.="" in="" the="" current="" study="" specific="" (soy)="" and="" non-specific="" (house="" dust)="" skin="" tests="" and="" immunoglobulins="" did="" not="" allow="" us="" to="" identify="" the="" workers="" at="" risk="" of="" developing="" symptoms="" or="" lung="" function="" abnormalities.="" this="" suggests="" that="" in="" addition="" to="" any="" atopic="" mechanisms,="" the="" irritant="" effect="" of="" soy="" dust="" may="" play="" a="" role="" in="" this="" occupational="" airway="">
Tubercle bacilli were preincubated with lecithin-cholesterol liposomes to be subsequently exposed to phospholipase A2. After further incubation in the environment of acidic buffer, viable units in the final mixture were enumerated by inoculating the serial dilutions of an aliquot onto Kirchner agar medium containing horse serum in 5%. Another aliquot was used for lipid analyses to confirm hydrolysis of lecithin. In addition to this bactericidal type of experiments, bacteriostatic tests were also conducted with Kirchner semi-solid agar medium, into which liposome-treated bacilli were inoculated with the enzyme at a time. Various natural and synthetic lecithins different in constituent fatty acids were employed. The results indicated that toxic fatty acids released from lecithin acted to kill the bacilli or to inhibit their growth.
The influence of treatment with polyunsaturated lecithin (EPL) and with saturated lecithin on the lipoprotein composition and fatty acid profile was investigated in 4 male chimpanzees. The animals were successively given 3 isocaloric diets containing the same amount of fat with a degree of saturation varying from 1 in the control diet to 0.2 in the diet enriched with polyunsaturated lecithin, to 4 in the diet enrich with saturated lecithin. The VLDL, LDL and HDL3 fractions were isolated by ultracentrifugal flotation; changes in their lipid and fatty acid composition were followed and their microviscosity was measured. The treatment with polyunsaturated lecithin increases the cholesterol esters and lysolecithin content in HDL3, presumably via activation of the enzyme LCAT. These modified HDL particles have a more fluid surface and a denser core and are susceptible to act as better cholesterol carriers. A complementary effect of this treatment is a decrease of the plasma triglycerides and VLDL concentration, an increase in the unsaturation ratio of the triglycerides which might take place via activation of triglyceride lipase. The saturated lecithin treatment increases the plasma VLDL and LDL concentrations and the triglyceride levels and increases mostly the saturation ratio of the cholesterol esters. These effects are likely to enhance the progression of atherosclerosis.
Forty commonly used inactivators, both simple substances and mixtures, were tested by a quantitative suspension test for the property of being non-toxic to the bacterial cell. Some inactivators proved to be too inhibitory, even for undamaged organisms, namely cysteine in concentrations of 1.0% and higher, 0.3% and 2.0% lecithin (both especially for P. aeruginosa), and the mixtures 0.3% lecithin/2.0% polysorbate 80/0.1% histidine/2.0% turkey-oil red (for St. aureus) and 0.3% lecithin/3.0% polysorbate 80/0.4% sodium laurylsulfate (for both test organisms).
The mechanism of intestinal absorption of polyunsaturated phosphatidylcholine in an oil medium was studied with 1,2-di-[9,10,12,13-3H4]linoleoyl-sn-glycero-3-phospho-[N-14CH3]-choline, 1-[1-14C]linoleoyl-2-[9,10,12,13-3H4]-linoleoyl- and 1-[9,10,12,13-3H4]linoleoyl-2-[1-14C]linoleoyl-sn-glycero-3-phosphocholine, especially with regard to the stability of the ester bonds in position 1 and 2 of the phospholipid molecule. The absorption rate, as measured by the disappearance from the gastro-intestinal tract, was comparatively rapid in the first 6 - 8 h, but then became considerably slower. After 24 h more than 90% of the applied radioactivity was absorbed from the intestinal tract. Respiratory 14CO2 from the degradation of the unsaturated acyl moiety in position 2 is produced much more rapidly than that from the acyl group attached to the 1-position of the glycerophosphocholine backbone. Analyses of the liver phosphatidylcholine by specific enzymatic hydrolysis with phospholipase A2, 6 h after the application, showed that in the isolated PC 9 times more labelled fatty acids from the original 1-position were present than from the corresponding 2-position. In rats with lymph fistula it was shown that more than 90% of the acyl moieties of the administered 1,2-di-[9,10,12,-13-3H4]linoleoyl-[N-14CH3] glycerophosphocholine was transported by the chylomicrons. About one half of the 14C choline radioactivity of the glycerophosphocholine backbone was found in the chylomicrons and the other half in the liver. The 3H radioactivity distribution in the chylomicrons amounted to 25% in the phosphatidylcholine fraction and 75% in the neutral lipids. Positional specific analyses of the phosphatidylcholine present in chylomicrons confirmed the fact that the 1-position remained practically intact while the 2-position underwent considerable exchange with unlabelled fatty acids. Analysis of the liver of the animals with lymph fistula indicated that it was practically free of the 3H radioactivity derived from the acyl moieties but contained a high percentage of the 14C radioactivity of the choline group. The methyl groups of choline were oxidized only to a very small extent. These results demonstrate that during the absorption process, about one half of the absorbed polyunsaturated phosphatidylcholine is hydrolyzed to 1-acyl-lysophosphatidylcholine and reacylated again to phosphatidylcholine upon entering the mucosa cell, while the other half is completely hydrolyzed to free fatty acids and glycerophosphocholine or its hydrolysis products. The fatty acids released are utilized for the reassembly of triacylglycerides and phosphatidylcholine found in the chylomicrons.
The formation of dimethylnitrosamine (DMNA) from choline chloride has been reported, Choline is commonly found as a component of lecithin. Since lecithin is present in animal tissue and is a widely used food additive, DMNA formation in foods containing both lecithin and nitrite is a pos-sibility. When 4.56 mmol of various natural lecithins and their components was allowed to react with sodium nitrite at pH 5.60 under model system conditions, DMNA was formed in varying concentrations (0.70 to 30.76 ppm).
Organogels obtained by adding small amounts of water to a solution of lecithin in organic solvents were studied as matrices for the transdermal transport of drugs. Gels obtained from isopropyl palmitate and cyclooctane were used (molar ratios of water to lecithin of 3 and 12, respectively). Preliminarily histological studies showed that the gels have no harmful effect when applied to the skin for prolonged periods. Data relative to the stability of the organogels with time are also presented. Scopolamine and broxaterol were used as model drugs, and the transdermal experiments were done with a Franz diffusion cell and human skin obtained from plastic surgery. The transport rate of scopolamine obtained with the lecithin gels was about one order of magnitude higher than that obtained with an aqueous solution of the drug at the same concentration. In contrast, the transport rates of scopolamine obtained with the microemulsion solution prior to gelation (molar ratio of water to lecithin, 0) were not different from those obtained with the gel. The same variations in transport rates were observed for broxaterol, in which case the flux through the skin was directly proportional to the concentration of drug in the gel. At a concentration of broxaterol of 75 mg/mL in the donor gel, the flux was 47 micrograms.h-1.cm-2. Because preliminary results showed that transdermal transport is successful with amino acids and peptides also, it is concluded that lecithin gels may be efficient vehicles for the transdermal transport of various drugs.
Cells of epithelial origin generally require ethanolamine (Etn) to grow in defined culture medium. When such cells are grown without Etn, the membrane phospholipid composition changes drastically, becoming phosphatidylethanolamine (PE)-deficient due to a reduced de novo rate of PE synthesis, and growth stops. We have hypothesized that the cessation of growth occurs because this membrane phospholipid environment is no longer suitable for membrane-associated functions. Phospholipid has long been known to play a role in the transduction of some signals across membranes. In addition to the well-known phosphatidylinositol cycles, hydrolysis of phosphatidylcholine (PC) and PE has recently been shown to play a central role in signal transduction. Using an Etn-requiring rat mammary cell line 64-24, we have studied the metabolism of PC and PE in response to the phorbol ester phorbol 12,13-dibutyrate (PDBu) under conditions where cells have either normal or PE-deficient membrane phospholipid. In cells having normal membrane phospholipid, the synthesis of PC was stimulated by PDBu (approximately fourfold), as was the degradation of PC and PE (by twofold and fourfold, respectively). Product analysis suggested that PDBu stimulated hydrolysis of PC by both phospholipases C and D (PLC and PLD), and of PE by PLD. However, in PE-deficient cells, neither lipid synthesis or degradation were significantly stimulated by PDBu. Analysis of the CDP-choline pathway of PC synthesis indicated that the regulatory enzyme, CTP:phosphorylcholine cytidylyltransferase, was stimulated about twofold by PDBu in cells having normal membrane, but not in PE-deficient cells. These results indicate that the membrane phospholipid environment profoundly affects phospholipid metabolism, which no doubt influences cell growth and regulation.
Gradients across the outer skin layers may result in fields enforcing a lipid flow into or through the intact skin surface provided that lipids are applied in the form of special vesicles. The osmotic gradient, for example, which is created by the difference in the total water concentrations between the skin surface and the skin interior, provides one possible source of such driving force. It is sufficiently strong to push at least 0.5 mg of lipids per hour and cm2 through the skin permeability barrier in the region of stratum corneum. The lipid concentration gradient, on the contrary, does not contribute much to the lipid penetration into dermis. Occlusion, therefore, is detrimental for the vesicle penetration into intact skin.
Addition of oleic acid to Krebs-II cells stimulated by 9-fold [3H]choline incorporation into choline glycerophospholipids without affecting the selective incorporation of the precursor into diacyl subclass (90% of total [3H]choline glycerophospholipids). The total activity of cytidylyltransferase (E.C. 2.7.7.15), the regulatory enzyme of choline glycerophospholipid synthesis, was increased in the particulate fraction at the expense of cytosol. Free [3H]oleic acid was also associated with the particulate fraction. Subcellular fractionation of membranes on Percoll gradient, indicated that the endoplasmic reticulum, which contained 90% of total cell free oleic acid, was the unique target for the translocation of cytidylyltransferase. [3H]oleic acid was incorporated almost exclusively into phosphatidylcholine and corresponded to a synthesis of 9 nmol/h per 10(6) cells. Based on [3H]choline incorporation a net synthesis of 22 nmol/h per 10(6) cells was determined. However, oleic acid treatment did not change the total amount of phosphatidylcholine (45 nmol/10(6) cells) and other phospholipids; also no modification in the subcellular distribution of phospholipids was observed. It is concluded that the stimulation of the de novo synthesis of phosphatidylcholine which involves translocation of cytidylyltransferase onto the endoplasmic reticulum, is accompanied by a renewal of their polar head group. Also exogenous oleic acid induces an enhanced fatty acid turnover, highly specific for phosphatidylcholine. Therefore, Krebs-II cells exhibited a high degree of regulation of their phosphatidylcholine content, suggesting a parallel stimulation of both synthesis and degradation.
Polyvinyl alcohol hydrogels which contained phospholipid, egg yolk lecithin or hydrogenated soya lecithin were designed as a transrectal delivery system for propranolol hydrochloride. The hydrogel preparations containing phospholipid were prepared by a low-temperature crystallization method. The release profile of propranolol from hydrogel preparations containing phospholipid complied with Fickian diffusion (Higuchi model). The release of propranolol from the hydrogel preparation decreased with higher contents of phospholipid (approximately 2% w/w). In rats plasma concentrations of propranolol after rectal administration of hydrogel preparations containing phospholipid (1 and 2% w/w) were prolonged compared with those of rats receiving preparations without phospholipid.
1,8-Dinitropyrene (1,8-DNP), present in polluted air, is a rodent carcinogen and a potent, direct-acting mutagen in salmonella typhimurium TA98. This mutagenicity is markedly reduced in the presence of mammalian hepatic S9 or microsomes. We demonstrate that at least a substantial part of this effect is attributable to non-enzymatic processes. The microsomal-dependent inhibition was unaffected by omission of an NADPH-generating system or when the cytochrome P-450 inhibitor, SKF-525A, or the cytochrome P-448 inhibitor, ellipticine, was incorporated in the metabolic activation system, suggesting that mixed function oxidases are not involved. Heat inactivation partially decreased the ability of induced S9 to reduce DNP mutagenicity. Substitution of S9 with a similar concentration of bovine serum albumin did not affect DNP activity. Thus non-specific binding to microsomal protein is not involved. However, when lipids, derived from uninduced microsomes, were added to incubations of DNP and S. typhimurium TA98, mutagenicity was decreased. Furthermore, substitution of microsomal lipids with a suspension of phosphatidylcholine (PC), a major lipid constituent of microsomes, affected DNP mutagenicity similarly. An increase in PC concentration resulted in a greater inhibitory effect. The reduction in DNP mutagenicity observed with microsomal lipids or with PC was less than that detected with uninduced S9, whilst the mutagenicity of 2-nitrofluorene was reduced to an approximately equal extent by lipids and S9. This phenomenon may be responsible for the S9-mediated detoxification of other mutagenic nitroaromatic compounds and may have important implications for mutagenicity testing.
Particulate drug carriers have a pronounced tendency to localize in the mononuclear phagocyte system and chronic administration of such carriers can result in reticuloendothelial (RE) blockade. In a previous study (Allen et al., J. Pharmacol. Exp. Therap., 229, 267, 1984) we have examined the ability of chronic i.v. administration of liposomes of a variety of compositions to cause RE blockade in mice. In this communication we report on the time course of histological changes in liver accompanying chronic liposome administration in samples collected at the time of our previous studies. The predominant histological feature was the appearance of a granulomatous reaction in liver. Granulomas were frequent in liver tissue of mice receiving 2 or more injections of sphingomyelin:phosphatidylcholine, 4:1 or distearoylphosphatidylcholine:cholesterol, 1:1 liposomes, but disappeared shortly after termination of liposome injections. In mice receiving phosphatidylcholine:cholesterol, 2:1 liposomes no granulomas in liver were apparent during the injection course (10 injections of 2 mg phospholipid each over 25 days) but granulomatous inflammation of the liver became apparent 2 weeks after the last injection and had not resolved by 9 weeks post-injection. The appearance of granulomas was correlated with depression of phagocytic index and their disappearance was correlated with normalization or stimulation of reticuloendothelial function. These observations may be related to the rate of phospholipid metabolism for the various phospholipid types or to the nature of phospholipid metabolites.
The absorption of indomethacin (IM) from suppositories containing hydrogenated soybean lecithin (HL) after rectal administration in rabbits was investigated with the aim of producing sustained-release suppositories. The suppositories were prepared by the fusion method with IM, HL and Witepsol H-15 (H-15). The IM release rate from the suppositories (IM 10 mg, HL 200 mg, total weight 1 g) was faster than that of the control suppositories without HL. The release of IM from the suppositories (IM 10 mg, HL 300 mg or 350 mg) showed slow-release profiles. In absorption studies in rabbits, sustained-plasma levels of IM were obtained when suppositories having an HL content of more than 300 mg were administered. The suppositories composed of Witepsol E-85 (melting point approximately 43 degrees C), 10 mg of IM, and 200 mg of HL, showed slow-release profiles in the release test, but did not show sustained plasma levels of IM in the absorption test. These results indicate that sustained-release suppositories able to release IM gradually from the surface of the suppositories can be obtained when HL, IM and H-15, whose melting point is lower than body temperature, are used in the preparation of the suppositories, provided that the HL content is high enough in relation to IM.
The toxic effects of hemolysed RBCs have been studied for more than 100 years, but the specific factors involved have not been identified. This study focused on phosphatidylethanolamine (PE) and phosphatidylserine (PS), two aminophospholipids that normally reside on the cytoplasmic side of the red cell membrane. An in vitro experiment with murine peritoneal exudate macrophages showed that PE and PS: a) stimulated the production of H2O2, complement factor C3a, prostacyclin, and thromboxane at a dose of 5 micrograms/ml; b) produced cell injury, evidenced by release of lipid peroxides, LDH, and by morphologic changes on phase-contrast and electron microscopy at a dose of 50 micrograms/ml; and c) caused cell death in 50-66% of cells at a dose of 100 micrograms/ml. An in vivo experiment showed that PE and PS injected intravenously into various groups of rabbits: a) caused only transient hypotension at a dose of 0.05 mg/kg body weight; b) caused significant hypotension, cardiac arrhythmias, bronchospasm, activation of intravascular coagulation, complement, platelets, and leukocytes with release of histamine, serotonin, and thromboxane at a dose of 0.10 mg/kg; and c) caused cardiac arrest and death at a dose of 0.30 mg/kg. In contrast, the phospholipids of the outer cell membrane (phosphatidylcholine and phosphatidylinositol) caused minimal toxicity in vitro and none in vivo.
A non-occluded multiple application skin blanching assay has been used to determine the effect of applied phosphatidylcholine (PC) on the bioavailability of corticosteroids. One forearm of each of ten volunteers was treated twice daily for one week with PC presented as a liposomal suspension in Sørensen's (pH 5.0) phosphate buffer (2.5 mg PC/0.5 mL) while the other arm was treated with 0.5 mL of phosphate buffer. For the following two weeks this treatment regimen was continued but in addition, each of four corticosteroid formulations (containing (i) hydrocortisone 0.1%, (ii) clobetasone butyrate 0.05%, (iii) betamethasone 0.1% and (iv) clobetasol propionate, 0.05%) was applied to sites on both arms. 5 +/- 1 mg of each cream was applied twice daily to the sites on day 1, then once daily for a further four days; after two days of no application, the protocol was repeated. Estimation of pallor was usually made four times daily. At the end of the second week of corticosteroid application the blanching response to all four formulations on the PC treated arms was significantly higher than on the buffer treated arm. Tachyphylaxis to the applied corticosteroids was markedly less apparent on the lipid-treated arms. It is proposed that the applied phospholipid either supplements the lipid content of the skin or provides a thin film in intimate epidermal contact. Such a film may promote hydration of the stratum corneum and also provide an environment into which corticosteroids initially partition before a subsequent, more controlled, release to the underlying tissue.
Lysophosphatidylcholine, arachidonic acid and docosahexaenoic acid were found to have a concentration-dependent inhibitory effect on the motility of human sperm, whilst phosphatidylcholine had no effect. Seminal plasma attenuated the sperm-immobilizing potencies of these lipids. Because all of the three inhibitors of motility are hydrolytic products of phosphatidylcholine, and the catalytic enzyme, phospholipase A2, is known to be calcium dependent, it is suggested that calcium might inhibit sperm motility by activating phospholipase A2 which in turn releases lysophosphatidylcholine and free fatty acids.
Ocular irritability of neutral or positively charged liposomes were assessed by the Draize test, histological examination and the rabbit blinking test. The mean total score (MTS) of the Draize test showed a slight increase immediately following instillation of liposome preparations. However, it did not exceed the "practically nonirritating level", and the MTS rapidly became less than the "nonirritating level". No corneal histological alteration was observed by optical microscopy following 9 instillations of each liposome preparation. Although the neutral liposome preparation failed to increase the rabbit blinking count, the positively charged liposome preparation did so to a significant degree. The neutral liposome preparation was confirmed not to give rise to ocular irritation. However, the positively charged liposome preparation may cause pain or unpleasantness following instillation.
The effects of non-drug-containing liposomes of different compositions and sizes on the proliferation of nine cancer-derived and one normal cultured human cell lines were determined. Stearylamine- and cardiolipin-containing liposomes were toxic (ID50) at 200 microM liposomal lipid concentrations or less, whereas phosphatidylglycerol- and phosphatidylserine-containing liposomes were toxic in the range 130-3000 microM. Phosphatidylcholine or dipalmitoylphosphatidylcholine liposomes were not toxic at 3000-4000 microM. In general, small liposomes were more toxic than large ones. The results indicate that there are wide variations in toxicity of non-drug-containing liposomes for cultured human cells. The potential for nonspecific toxicity due to the liposomes themselves should be carefully considered if human administration of drug-containing liposomes is to be done.
Beta-adrenergic agonists in metered dose inhalers (MDIs) are used extensively in the treatment of asthma. Previously we reported that 23 of 1450 (1.6%) of our asthmatic patients experienced immediate bronchoconstriction after using MDI-albuterol. In this study we investigated immediate bronchoconstriction after use of MDI-metaproterenol and after placebo-inhaler with "inert ingredients" only. Results suggest that those patients who complained of chest tightness or lack of relief following the use of MDI beta-adrenergic agonists are having true bronchoconstriction. The bronchoconstrictive response is most likely caused by the propellants or the other inert ingredients contained in these MDIs.
