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In vivo anti-melanogenesis activity and in vitro skin permeability of niacinamide-loaded flexible liposomes (BounsphereTM)
Abstract
This study was conducted to evaluate preparation and characteristics of flexible liposomes (Bounsphere™) consisting of a biocompatible lipid membrane with dipotassium glycyrrhizate (DPG) as an edge activator and containing niacinamide (NA). We evaluated particle size and zeta potential of the prepared liposomes by dynamic light scattering (DLS), and investigated their deformability, safety, skin permeability, and anti-melanogenesis activity in Bounsphere™ that remained stable for more than 6 months. The average size of Bounsphere™ was about 200 nm, and the change in liposome size after 6 months was not greater than that of conventional liposomes. The zeta potential of Bounsphere™ was about 32 mV with a positive charge, indicating relatively good stability. The deformability of Bounsphere™ was higher than that of conventional liposomes. In addition, the skin permeability of Bounsphere™ was higher than that of conventional liposomes or the phosphate buffer solution. These results indicated that Bounsphere™ with DPG as an edge activator has advantages over conventional liposomes as NA carriers. Furthermore, we found that 2% NA-loaded Bounsphere™ enhanced skin whitening. Taken together, our results demonstrate that Bounsphere™ can be used as a delivery system to enhance transdermal permeation and skin whitening agent effectiveness.
... Further, when surfactants enter the lipid bilayer, they reduce the bending energy of the bilayer. Compared to traditional liposomes, flexible liposomes exhibited a characteristic fluid membrane with high elasticity, facilitating the permeation of many molecules through the stratum corneum and cell membranes of the skin [30,31]. This property makes them suitable for transdermal drug delivery while minimizing the risk of drug leakage [32]. ...
... This property makes them suitable for transdermal drug delivery while minimizing the risk of drug leakage [32]. The surfactants in flexible liposomes reduced the interfacial tension of the bilayer that increased the bilayer fluidity in the stratum corneum and enhanced the permeability of liposomes encapsulating drugs into the skin [31,33]. Further, flexible liposomes easily reach the dermis and locally release the drug due to lysosomal degradation [34]. ...
Curcumin is utilized extensively as Chinese medicine in Asia due to its antioxidant, antimicrobial, and inflammatory activities. However, its use has the challenges of low oral bioavailability and high heat sensitivity. The aim of this research was to produce flexible nano-liposomes containing curcumin using an innovative approach of ethanol injection and Tween 80 to enhance the stability and preservation of curcumin. The mean particle size, encapsulation efficiency, thermal degradation, storage stability, and curcumin release in flexible nano-liposomes were also investigated. We found that the mean particle size of curcumin-loaded flexible nano-liposome decreased from 278 nm to 27.6 nm. At the same time, the Tween 80 concentration increased from 0 to 0.15 wt%, which corresponded with the results of transmission electron microscopy (TEM) morphology analyses, and particle size decreased with an enhancement in Tween 80 concentration. Further, pure curcumin was quickly released within one hour at 37 °C, and first-order kinetics matched with its release curve. However, curcumin encapsulated in flexible nano-liposomes showed a slow release of 71.24% within 12 h, and a slower release pattern matched with the Higuchi model over 24 h, ultimately reaching 84.63% release. Hence, flexible nano-liposomes of curcumin made by a combination of ethanol injection and Tween 80 addition prevented the thermal degradation of curcumin, and enhanced its storage stability and preservation for future drug delivery applications.
... Other vesicular carriers [57,122] such as bilosomes, cubosomes, vesosomes, novasomes, lipid vesicular gels are new-generations vesicles owing advantages over liposomes as delivery systems in cosmetics; nevertheless, this category is not be developed in this review. Some examples of studies [123][124][125][126][127][128][129][130] illustrating the great potential of transferosomes, ethosomes and niosomes over conventional liposomes as delivery systems for cosmetic skin applications, are detailed in the following section. ...
... Lee et al. [123] developed a flexible liposome system (Bounsphere™) loaded with niacinamide (NA), a cosmetic skin-whitening agent, to improve both the skin permeability of NA and the anti-melanogenesis properties of NA. These liposomes were composed of a lipid membrane with additional dipotassium glycyrrhizate as an edge activator. ...
Nowadays, there is a growing demand for effective cosmetic skincare products that can address the specific skin problems of consumers. Delivery systems play an important role in the effective action of cosmetic skincare formulations. Delivery systems are attractive and smart technologies used as carriers for cosmetic ingredients, which are sensitive to various physical factors such as light, oxygen, pH and temperature. Delivery systems offer several advantages: transport and protection of sensitive active compounds, controlled and targeted release of active ingredients. Several delivery systems, varying in chemical composition, with adaptable physicochemical characteristics (size, morphology, zeta potential, structure) as well as great advantages as carriers, are developed and described in the literature. This article reviews the current cosmetic active ingredients used in skincare products due to their beneficial properties such as antioxidant, anti-aging, photo-protective, anti-inflammatory, anti-microbial, etc.). In addition, the main advantages of several classes of delivery systems (emulsions, lipid nanoparticles, polymeric particles) are described, as well as some recent approaches used to ensure their efficacy (long-term stability, controlled release of the active, skin penetration/permeation) are reviewed. Finally, new trends to be considered for the development of delivery systems and cosmetic formulations are discussed.
... In order to improve the efficacy of the drug at the target site and to achieve prolonged release effect, the incorporation of niacinamide in liposomes, microemulsions, and nanofibers is appreciated. [13][14][15] • The major challenge in utilizing hydrophilic molecule vitamin C is to maintain its stability. Vitamin C rapidly degrades in the aqueous medium, at high pH, in the presence of oxygen and metal ions. ...
... In vivo skin whitening effect and safety were evaluated on 21 patients with melasma, which demonstrated a significant skin whitening effect after 4 to 8 weeks of application with no skin irritancy. [13] Boonme, et al. formulated the microemulsion of nicotinamide that enhanced the penetration of active into the skin. Nicotinamide microemulsion was fabricated using isopropyl palmitate, Span 80, and Tween 80. ...
Cosmeceuticals are cosmetic products with biologically active ingredients purporting to have drug-like benefits. Cosmeceuticals are one of the fastest-growing segments of the personal care industry as their use has drastically increased over the years. Vitamins being one of the popular ingredients in cosmeceuticals have numerous skin benefits. Vitamins are organic micronutrients essential for the proper functioning of the body. The popular vitamins used in cosmetics are vitamin A, vitamin B 3, vitamin C, vitamin E, and vitamin K. These vitamins play an important role in treating skin conditions like acne, hyperpigmentation, and photoaging, protecting from UV, deactivating free radicals, and improving skin moisture retention levels of the skin. This review article emphasizes on the novel formulation of the vitamins-based cosmeceuticals. The novel carriers system has gained importance in cosmetic delivery due to its advantages such as enhanced skin penetration, sustained and controlled drug release profile, maintenance of the concentration within the therapeutic range, with greater safety and targeted delivery of active to the desired tissues. © 2021 Journal of Reports in Pharmaceutical Sciences Published by Wolters Kluwer-Medknow.
... Lee et al. [81] designed deformable liposomes or transferosomes (Bounsphere™) by dispersing the oil phase (hydrogenated lecithin, ceramide, cholesterol and glycerol) containing edge activator (dipotassium glycyrrhizate) into the water phase containing niacinamide (2%) before passing through a microfluidiser to form a fine suspension. The presence of dipotassium glycyrrhizate allowed Bounsphere™ to achieve a smaller particle size (197.2 ...
Niacinamide, an active form of vitamin B3, is recognised for its significant dermal benefits including skin brightening, anti-ageing properties and the protection of the skin barrier. Its widespread incorporation into cosmetic products, ranging from cleansers to serums, is attributed to its safety profile and proven efficacy. Recently, topical niacinamide has also been explored for other pharmaceutical applications, including skin cancers. Therefore, a fundamental understanding of the skin permeation behaviour of niacinamide becomes crucial for formulation design. Given the paucity of a comprehensive review on this aspect, we provide insights into the mechanisms of action of topically applied niacinamide and share the current strategies used to enhance its skin permeation. This review also consolidates clinical evidence of topical niacinamide for its cosmeceutical uses and as treatment for some skin disorders, including dermatitis, acne vulgaris and actinic keratosis. We also emphasise the current exploration and perspectives on the delivery designs of topical niacinamide, highlighting the potential development of formulations focused on enhancing skin permeation, particularly for clinical benefits.
... The amount of melanin (M-values) in the skin after 4 weeks and 8 weeks was remarkably increased by 9.96% and 16.80%, respectively, with negligible irritation potential compared with the M-values before NA treatment. 45 The liposomes loaded anthocyanin showed suppression of tyrosinase, MTFF (Microphthalmia-associated transcription factor protein expression) and melanogenesis when studied on Human A 375 melanocytes. The DPPH scavenging activity of liposome-encapsulated anthocyanin was found to be 64% at a concentration of 20 mg/ml and 76% at 50 mg/ml. ...
... In 2018, Limsuwan and his colleagues investigated that transferosomes demonstrated improved solubility and stability of phenylethyl resorcinol [70]. The niacinamide loaded transferosomes improved skin permeability, solubility, stability, and whitening efficacy in comparison to regular liposomes [71]. In another research, it was investigated whether arbutin-loaded transferosomes exhibited improved skin permeation and the deposition of hydrophilic skin-whitening compounds [72]. ...
The abundant synthesis and accretion of melanin inside skin can be caused by activation of melanogenic enzymes or increase in number of melanocytes. Melasma is defined as hyperpig-mented bright or dark brown spots which are symmetrically distributed and have serrated, and irregular borders. The three general categories of pigmentation pattern include centro facial pattern, malar pattern and mandibular pattern. Exposure to UV rays, heat, use of cosmetics and photosen-sitizing drugs, female sex hormonal therapies, aberrant production of melanocyte stimulating hormone and increasing aesthetic demands are factors which cause development of melasma disease. This review gives brief overview about fitzpatrick skin phototype classification system, life cycle of melanin, mechanism of action of anti-hyperpigmenting drugs and existing pharmacotherapy strategies for treatment of melasma. The objectives of this review are focused on role of cutting-edge nanotechnology based strategies like lipid-based nanocarriers i.e. lipid nanoparticles, microemul-sions, nanoemulsions, liposomes, ethosomes, niosomes, transfersomes, aspasomes, invasomes penetration enhancing vesicles; inorganic nanocarriers i.e. gold nanoparticles, fullerenes and polymer-based nanocarriers i.e. polymeric nanoparticles, polymerosomes and polymeric micelles for management of hyperpigmentation.
... Drug delivery systems emerged as a tool to overcome NIA's physicochemical properties that hinder its penetration through the skin. Lee et al. studied the skin permeability and the anti-melanogenesis activity of NIA by incorporating it into flexible liposomes with the edge activator dipotassium glycyrrhizate, proving that the skin permeability of NIA in these flexible liposomes was significantly higher than that of the conventional liposomes [18]. Offerta and co-workers evaluated different strategies to optimize the percutaneous absorption of NIA and soy phytosterols by making use of solid lipid nanoparticles and penetration enhancers such as hydrogenated lecithin [6]. ...
Niacinamide (NIA) has been widely used in halting the features of ageing by acting as an antioxidant and preventing dehydration. NIA’s physicochemical properties suggest difficulties in surpassing the barrier imposed by the stratum corneum layer to reach the target in the skin. To improve cutaneous delivery of NIA, a hybrid nanogel was designed using carrageenan and polyvinylpyrrolidone polymers combined with jojoba oil as a permeation enhancer. Three different types of transethosomes were prepared by the thin-film hydration method, made distinct by the presence of either an edge activator or a permeation enhancer, to allow for a controlled delivery of NIA. Formulations were characterized by measurements of size, polydispersity index, zeta potential, encapsulation efficiency, and loading capacity, and by evaluating their chemical interactions and morphology. Skin permeation assays were performed using Franz diffusion cells. The hybrid hydrogels exhibited robust, porous, and highly aligned macrostructures, and when present, jojoba oil changed their morphology. Skin permeation studies with transethosomes-loaded hydrogels showed that nanogels per se exhibit a more controlled and enhanced permeation, in particular when jojoba oil was present in the transethosomes. These promising nanogels protected the human keratinocytes from UV radiation, and thus can be added to sunscreens or after-sun lotions to improve skin protection.
... To increase the skin penetration of drugs, various strategies have been used, such as microemulsions [8], liposomes [9], ultrasound [10], nanofibers [11], niosomes [12], and magnetophoresis [13]. Liposomes are spherical phospholipid bilayer nanoparticles that can entrap both hydrophilic and lipophilic drugs. ...
This study aimed to develop ultradeformable liposomes (ULs) with fatty acids, namely, oleic, linoleic, and linolenic acid, to improve the skin penetration of rosmarinic acid. This study also investigated the vesicle-skin interaction and skin penetration pathway of ULs with fatty acids using the co-localization technique of multifluorescently labeled particles. The prepared ULs were characterized in terms of size, surface charge, size distribution, shape, % entrapment efficiency (% EE), and % loading efficiency (% LE). The prepared ULs with fatty acids had an average particle size between 50.37 ± 0.3 and 59.82 ± 17.3 nm with a size distribution within an acceptable range and exhibited a negative surface charge. The average % EE and % LE were 9 and 24.02, respectively. The in vitro skin penetration study found that ULs with oleic acid could significantly increase the skin penetration of rosmarinic acid compared to ULs. According to confocal laser scanning microscopy observations, this study suggested that UL vesicles attach to the skin before releasing the entrapped drug to penetrate the skin. These findings suggested that ULs with oleic acid penetrated the skin via the transfollicular pathway as a major penetration pathway.
... Therefore, the skin penetration efficiency of nicotinamide is limited. Overcoming the hydrophobic skin barrier, ternary microemulsion systems and W/O/W multiple emulsion systems [8], flexible liposome systems [9], and binary and ternary solvent systems [10] have been developed. These drug carriers and solvents enhanced the nicotinamide penetration into the animal skins 2-to 10-fold compared with the control solutions; however, the nicotinamide concentrations in the carriers/solvents were as high as 2 to 5%. ...
Objective
Nicotinamide, also known as niacinamide, is a water‐soluble vitamin that is used to prevent and treat acne and pellagra. It is often found in water‐based skin care cosmetics because of its high water‐solubility. Nicotinamide is a small molecule with a molar mass of 122.1 g/mol. However, it has a hydrophilic nature that becomes an obstacle when it penetrates through the skin. The topmost layer of the skin, the stratum corneum, acts as a strong hydrophobic barrier for such hydrophilic molecules. The oil‐based formulations are expected to enhance the transdermal delivery efficiency of nicotinamide.
Methods
We have developed oil‐based microemulsion formulations composed of a squalane‐vehicle. Monoolein was used as an emulsifier that has a potential to enhance the nicotinamide delivery through the stratum corneum.
Results
Because the mean size of the emulsions measured by dynamic light scattering was 20.9 ± 0.4 nm, the microemulsion formulation was stable under the long‐term storage. Monoolein acted as a skin penetration enhancer, and it effectively enabled the penetration of nicotinamide through human abdominal skin, compared with nicotinamide in a phosphate buffered saline solution. The flux was increased 25‐fold. Microscopic imaging revealed that the hydrophilic bioactive compounds penetrated through the intercellular spaces in the epidermis.
Conclusion
The monoolein‐based microemulsion was transparent and stable, suggesting that it is a promising formulation for a transdermal nicotinamide delivery.
... In this study, data from 17,019 Korean women were used to conduct GWAS analysis using the Illumina Global Screening Array MD BeadChip (Illumina, San Diego, CA) to identify the genetic variants associated with facial pigmented spots and to validate the genetic effects of the variants. The measurement of facial pigmented spots was conducted using the Janus 3 system (PIE, Suwon, Korea), which is one of the most widely used image analysis devices in the field of skin research in Korea (Goo et al., 2015;Kim et al., 2016;Lee et al., 2016;Leem et al., 2020;Sim et al., 2014). ...
Variation in skin pigmentation can be affected both by environmental factors and intrinsic factors such as age, gender, and genetic variation. Recent genome-wide association studies (GWASs) revealed that genetic variants of genes functionally related to a pigmentation pathway were associated with skin pigmentary traits. However, these GWAS focused on populations with European ancestry and only a few studies have been performed on Asian populations, limiting our understanding of the genetic basis of skin pigmentary traits in Asians. To evaluate the genetic variants associated with facial pigmented spots, we conducted a GWAS analysis of objectively measured facial pigmented spots in 17,019 Korean women. This large-scale GWAS identified several genomic loci that were significantly associated with facial pigmented spots (five previously reported loci and two previously unreported loci to our knowledge), which were detected by UV light; BNC2 at 9p22 (rs16935073; P-value = 2.11×10⁻⁴⁶), PPARGC1B at 5q32 (rs32579; P-value = 9.04×10⁻⁴²), 10q26 (rs11198112; P-value = 9.66×10⁻³⁸), MC1R at 16q24 (rs2228479; P-value = 6.62×10⁻²¹), lnc01877 at 2q33 (rs12693889; P-value = 1.59×10⁻¹¹), CDKN2B-AS1 at 9p21 (rs643319; P-value = 7.76×10⁻⁹), and MFSD12 at 19p13 (rs2240751; P-value = 9.70×10⁻⁹). Further functional characterization of the candidate genes needs to be done to fully evaluate their contribution to facial pigmented spots.
... NIA has been demonstrated to have a number of anti-inflammatory and photo-protective effects following topical application. The therapeutic benefits of NIA in the management of acne and atopic dermatitis and promotion of the up-regulation of epidermal lipid synthesis have also been reported [3,4]. Mohammed, et al. [5] investigated the influence of NIA on the molecular properties of the human stratum corneum (SC) in vivo. ...
Niacinamide (NIA) is the amide form of vitamin B3 and has been widely used in pharmaceutical and personal care formulations. Previously, we reported a comparative study of NIA permeation from neat solvents using the Skin Parallel Artificial Membrane Permeability Assay (PAMPA) and mammalian skin. A good correlation between NIA permeation in the different models was found. In the present work, ten binary and ternary systems were evaluated for their ability to promote NIA delivery in the Skin PAMPA model, porcine skin and human epidermis. Penetration enhancement was evident for binary systems composed of propylene glycol and fatty acids in human skin studies. However, propylene glycol and oleic acid did not promote enhancement of NIA compared with other systems in the Skin PAMPA model. A good correlation was obtained for permeation data from Skin PAMPA and porcine skin. However, data from the Skin PAMPA model and from human skin could only be correlated when the PG-fatty acid systems were excluded. These findings add to our knowledge of the potential applications of Skin PAMPA for screening dermal/transdermal preparations.
... Niacinamide (NIA), is the amide form of vitamin B3 and is a hydrophilic compound with a low molecular weight (Table 1). It is used in cosmetic and personal care formulations for the management of a number of dermatological conditions, including melanogenesis, acne, atopic dermatitis, aging of the skin and ultraviolet-induced DNA damage (Lee et al., 2016;Papich, 2016). Mohammed et al. (2013) volume was set to 10 L. ...
The in vitro skin penetration of pharmaceutical or cosmetic ingredients is usually assessed in human or animal tissue. However, there are ethical and practical difficulties associated with sourcing these materials; variability between donors may also be problematic when interpreting experimental data. Hence, there has been much interest in identifying a robust and high throughput model to study skin permeation that would generate more reproducible results. Here we investigate the permeability of a model active, niacinamide (NIA), in (i) conventional vertical Franz diffusion cells with excised human skin or porcine skin and (ii) a recently developed Parallel Artificial Membrane Permeation Assay (PAMPA) model. Both finite and infinite dose conditions were evaluated in both models using a series of simple NIA solutions and one commercial preparation. The Franz diffusion cell studies were run over 24 h while PAMPA experiments were conducted for 2.5 h. A linear correlation between both models was observed for the cumulative amount of NIA permeated in tested models under finite dose conditions. The corresponding correlation coefficients (r²) were 0.88 for porcine skin and 0.71 for human skin. These results confirm the potential of the PAMPA model as a useful screening tool for topical formulations. Future studies will build on these findings and expand further the range of actives investigated.
There are millions of people suffering from acquired hyperpigmentation
diseases such as melasma all over the world. The appearance of melasma is
indicated by symmetrical, hyperpigmented patches and macules that can take on
several forms, such as blotchy, irregular, arcuate, and polycyclic. Hormonal
treatments (including oral contraceptives), pregnancy, antiepileptic drugs, intense
sun exposure, phototoxic substances, and genetic predisposition are common
triggers of melasma. There are several treatments available for patients who are
suffering from melasma. Typically, first-line treatments include medications that
influence the route where pigment is produced, broad-spectrum photoprotection,
and camouflage. Chemical peels are frequently included in second-line treatment,
albeit patients with darker skin should use caution while using them. While carrying
a high risk of making the disease worse, laser and light therapy are potentially viable
options for people who have failed previous treatments. There is a need for an
alternative strategy with fewer side effects and high success rates because of several
shortcomings and consequences of existing treatments. Novel approaches,
including microemulsions, nanoemulsions, solid lipid nanoparticles, nanostructured
lipid carriers, liposomes, niosomes, transfersomes, aquasomes, ethosomes,
penetration enhancer vesicles, chitosan nanoparticles, ethyl cellulose nanoparticle,
and fullerene, lead to greater effectiveness, quicker recovery, and higher patient
satisfaction.This review summarizes the novel approaches and clinical trials used
for the management of melasma.
Melasma is a chronic hyperpigmentation skin disorder that is more common in the female gender. Although melasma is a multifactorial skin disorder, however, sun-exposure and genetic predisposition are considered as the main etiologic factors in melasma occurrence. Although numerous topical and systemic therapeutic agents and also non-pharmacologic procedural treatments have been considered in melasma management, however, the commonly available therapeutic options have several limitations including the lack of sufficient clinical effectiveness, risk of relapse, and high rate of unwanted adverse drug reactions. Recruitment of nanotechnology for topical drug delivery in melasma management can lead to enhanced skin penetration, targeted drug delivery to the site of action, longer deposition at the targeted area, and limit systemic absorption and therefore systemic availability and adverse drug reactions. In the current review, first of all, the etiology, pathophysiology, and severity classification of melasma have been considered. Then, various pharmacologic and procedural therapeutic options in melasma treatment have been discussed. Afterward, the usage of various types of nanoparticles for the purpose of topical drug delivery for melasma management was considered. In the end, numerous clinical studies and controlled clinical trials on the assessment of the effectiveness of these novel topical formulations in melasma management are summarized.
Recent advances in enzymatic biofuel cells (EBFCs) have resulted in great progress in health monitoring and supplying power to medical applications, such as drug delivery. On the other hand, to enhance the electric field-assisted transdermal permeation for facial mask application, an external power source is usually required. Herein, we attempted to combine an EBFC with a facial mask so that the microcurrent generated can boost the transdermal permeability of target molecules in the facial mask essence. When screen-printed onto a polypropylene-based non-woven fabric, the three-layered flexible EBFC could produce a voltage of ∼0.4 V and a maximum power density of 23.3 μW cm-2, leading to an approximately 2-3-fold increase in permeated nicotinamide, arbutin, and aspirin levels within 15 min compared to non-iontophoretic transdermal drug delivery. Both cell viability and animal experiments further demonstrated that the EBFC-powered iontophoresis worked well in living animals with good biocompatibility. These results suggest that the EBFC-powered iontophoretic facial mask can effectively improve the permeation of drugs and holds a promise for the possible cosmetic application.
For most external applied antioxidant whitening ingredients, effective stratum corneum breakthrough, epidermal penetration and dermal deposition are necessary premises for inhibition of melanin production and transfer occurring in stratum basale. Herein, xanthan gum was added into vitamin C-containing flexible liposome (Vc-L) suspension. The long polymer chain of xanthan gum string dispersed Vc-L together to gain a lotion (Vc-LX) for external application. In this study, the storage stability experiments demonstrated that the additional xanthan gum could improve the storage stability of Vc liposome suspension. The cumulative in vitro skin penetration and deposition of Vc-LX was found to significantly increase within 24 h in mouse skin, compared with those of the Vc aqueous solution and Vc conventional liposomes treated groups (***p < 0.001). Most importantly, in vivo skin whitening experiments gave that Vc-LX has better skin whitening activity (ΔL*) than marketed products (GARNIER® Vc377), Vc flexible liposomes, and Vc conventional liposomes. Moreover, in vitro cytotoxicity experiments and skin irritation experiments demonstrated that Vc-LX has good biosafety. Therefore, this study suggested that Vc-LX may be a promising local skin delivery system for water-soluble antioxidant ingredients.
Background:
Cationic liposomes can enhance the permeability of drugs in 3-D skin. Chitosan is considered a safe material for percutaneous delivery, thus this study use chitosan-incorporated cationic liposomes.
Aims:
This study investigated the improvement in skin brightness, melanin and melasma after treatment niacinamide-incorporated chitosan cationic liposomes.
Methods:
A skin brightening agent, niacinamide, was formulated into cationic liposomes to facilitate percutaneous absorption and was clinically tested in 21 Korean female subjects. Cationic liposomes were prepared using a high-pressure homogenizer after mixing an oil phase containing lecithin and cholesterol and an aqueous phase containing niacinamide and chitosan.
Results:
The cationic liposomes exhibited stability over 28 days, with a particle size of 255-275 nm and zeta potential of 10-14 mV. Cationic liposomes containing niacinamide and a control formulation were applied to the left and right side of the face, respectively, twice daily for 28 days. Skin brightness, melanin index, and area of melasma were significantly enhanced where cationic liposomes were used, in comparison with formulations without cationic liposomes, demonstrating a 1.38-2.08-fold improvement.
Conclusion:
Thus, we established that chitosan liposomes augmented the percutaneous absorption of niacinamide and improved the appearance of the skin.
Melanin is a kind of dark insoluble pigment that can cause pigmentation and free-radical clearance, inducing melasma, freckles, and chloasma, affecting the quality of life of patients. Due to poor water solubility and low safety, the absorption of poorly water-soluble drugs is limited by the hinderance of a skin barrier. Therefore, it is necessary to develop new, safe, and highly efficient drugs to improve their transdermal absorption efficiency and thus to inhibit the production of melanin. To address these issues, we developed a new nicotinamide (NIC)-stabilized phloretin nanocrystals (PHL-NCs). First, NC technology significantly increased the solubility of PHL. The in vitro release results indicated that at 6 h, the dissolution of the PHL-NIC-NCs was 101.39% ± 2.40% and of the PHL-NCs was 84.92% ± 4.30%, while that of the physical mixture of the two drugs was only 64.43% ± 0.02%. Second, NIC acted not only as a stabilizer to enlarge the storage time of PHL-NIC-NCs (improved to 10-day in vitro stability) but also as a melanin transfer inhibitor to inhibit melanin production. Finally, we verified the melanin inhibition effect of PHL-NIC-NCs evaluated by the zebrafish model. It showed that 0.38 mM/L PHL-NIC-NCs have a lower tyrosinase activity at 62.97% ± 0.52% and have less melanin at 36.57% ± 0.44%. The inhibition effect of PHL-NCs and PHL-NIC-NCs was stronger compared to the positive control arbutin. In conclusion, the combination of NIC and PHL achieves better inhibition of tyrosinase and inhibition of melanin production through synergism. This will provide a direction to the subsequent development of melanin-inhibiting drugs and the combined use of pharmaceutical agents.
Introduction: Melasma is a very common and difficult to treat hypermelanosis because it usually responds poorly to therapies, negatively affecting the quality of life of patients. Objective: to know and analyze the scientific evidence related to the treatment of patients with facial melasma treated with niacinamide. Method: a literature review was performed based on a data search in BIREME, PubMed, SciELO and ScienceDirect. Articles indexed in these electronic journals were included in the time frame from 2011 to 2019. Results: Evidence analyzes revealed a major impact on the appearance of facial melasma after niacinamide treatment. Well, the studies (100%) concluded improvement of the spots with the treatment time, improving the appearance of the skin. Conclusion: Evidence shows that niacinamide has a lightening property in adult women with improvement of melanic hyperpigmentation caused by melasma. However, there is very little evidence published in the last decade using pure niacinamide for increased pigmentation in melasma.
Sekarang ini adanya keinginan alamiah untuk tampil cantik khususnya pada kaum wanita telah meningkatkan kesadaran tentang pentingnya perawatan kulit dan warnanya, untuk itu upaya yang dapat dilakukan adalah memutihkan kulit dengan menekan produksi melanin menggunakan whitening agent, sehingga dilakukan penulisan artikel review ini dengan tujuan mengetahui jenis-jenis whitening agent, mekanismenya dan penggunaan teknologi formulasinya. Beberapa contoh whitening agent yaitu hydroquinone, ascorbic acid, kojic acid, arbutin, niacinamide, retinoid, azelaic acid, namun beberapa zat ini dapat menimbulkan permasalahan pada kulit seperti iritasi, dermatitis, alergi dan kanker kulit sehingga sekarang ini dapat digunakan whitening agent dari alam yang minim efek samping seperti temulawak, cendana, teripang, dan prunus. Mekanisme utama whitening agent adalah menghambat enzim tirosinasedan, dan untuk memaksimalkan efek whitening pada kulit telah dikembangkan teknologi formulasi menggunakan beberapa metode penghantaran seperti liposom, nanopartikel, solid lipid nanopartikel dan mikroemulsi.
Extensive melanin production and accumulation inside the skin may result in a number of disorders, among which is acquired hyperpigmentation, such as melasma. Skin hyperpigmentation is attributed to either the increase in the number of melanocytes or the hyperactivity of melanogenic enzymes. Genetic susceptibility, ultraviolet radiation, hormonal remedies as well as the abnormal release of the α-melanocyte stimulating hormone (α-MSH) represent the provoking factors contributing to such disorder. On the account of their prominent localization in skin-exposed areas, hyperpigmentation may possess cosmetic and psychosocial relevance, and subsequently many efforts have been exerted to help rectify this skin disorder. The current review presents the approaches adopted to treat melasma. It also reviews the active molecules counteracting the melanogenesis process and the diverse nanotechnology-based delivery systems, which showed successful topical delivery of hypopigmenting agents for the treatment of melasma.
Background
The Janus‐III measurement system evaluates the overall skin characteristics such as skin pore, wrinkle, sebum, porphyrin, skin pigmentation, and skin color using high‐resolution facial images. The values are measured from five different facial areas, namely, the forehead, nose, corner of/skin below the eyes, and cheeks. Owing to its convenience and diverse measuring characteristics, Janus‐III has been widely used in skin research and the cosmetic industry in Korea. In our previous study, we revealed the consistency and reliability of the system with repeatedly measured values. Its measuring performance was investigated statistically, but to make it more reliable for academic skin research, additional verification by a professional dermatologist is needed.
Materials and Methods
In this study, we conducted comparative analysis of three skin characteristics (pigmented spot, skin color, and eye wrinkle) by a dermatologist and the Janus‐III measurement system. We utilized 330 image data that were cropped from the whole facial images of 330 different participants to avoid correlation among the three measuring items. Pearson's correlation coefficient exhibited similar patterns between the system and the dermatologist's findings.
Results
The main finding of our study was that the measured value of skin characteristics by the Janus‐III system showed clear correlation with the values evaluated by a dermatologist, especially in a pigmented spot.
Conclusion
Therefore, it would be a plausible idea to consider the Janus‐III system for specialized research of skin characteristics even with a small sample size.
Background:
For personalized skin care, noninvasive quantitative methods to evaluate facial skin characteristics are important. Janus-III is one of the most widely used imaging analysis devices in the skin care industry in Korea. Janus-III generates values for a range of skin characteristics. Due to the convenience of obtaining results for a variety of skin characteristics in a single measurement, the use of Janus-III in cosmetic stores and research institutes has been recently increasing. However, the consistency of skin measurements of Janus-III has not been elucidated yet.
Materials and methods:
In this study, we repeated skin measurements three times for 70 different subjects and compared each numerical value in order to assess the consistency of the Janus-III. For this purpose, we compared between-sample distances and within-sample distances.
Results:
We found important patterns for future analyses in terms of consistency. First, the average values of skin measurement categories were more reliable than individual part values of facial segments. Second, center part values such as forehead and nose were more reliable than side part values such as left and right part segments.
Conclusion:
If researchers who use Janus-III for studies of facial characteristics analyze average and center part values first, they can obtain relatively reliable patterns of facial skin characteristics.
In the present scenario consumers are searching for personal care products that supply multiple benefits with minimal efforts. The outcome has been the introduction of nanotechnology based cosmetic products that are safe to use and results driven. Some topical cosmetics can act efficaciously when they reach their target sites present in the deeper layers of the skin. The main problem with delivering active ingredients across the skin is the barrier function of the skin. Therefore to get the maximum benefit from cosmetic products and to overcome the problems associated with their skin penetration, scientists are investigating various strategies to overcome these barrier properties. Vesicular carriers have been claimed to improve the topical delivery of active ingredients. This review offers a brief overview of current approaches in the research and development of vesicular carriers to improve the delivery and performance of active ingredients present in the cosmetics.
Skin whitening products are commercially available for cosmetic purposes in order to obtain a lighter skin appearance. They are also utilized for clinical treatment of pigmentary disorders such as melasma or postinflammatory hyperpigmentation. Whitening agents act at various levels of melanin production in the skin. Many of them are known as competitive inhibitors of tyrosinase, the key enzyme in melanogenesis. Others inhibit the maturation of this enzyme or the transport of pigment granules (melanosomes) from melanocytes to surrounding keratinocytes. In this review we present an overview of (natural) whitening products that may decrease skin pigmentation by their interference with the pigmentary processes.
Liposomes are microparticulate lipoidal vesicles which are under extensive investigation as drug carriers for improving the delivery of therapeutic agents. Due to new developments in liposome technology, several liposome-based drug formulations are currently in clinical trial, and recently some of them have been approved for clinical use. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.
Melasma is a common disorder of hyperpigmentation affecting millions of people worldwide. While it is thought to be triggered or exacerbated by sun exposure and hormones, much remains to be understood about its pathogenesis. A thorough understanding of the etiology of melasma and the research tools available to study this condition are crucial to enhancing management and developing novel targeted therapies of this often frustrating condition.
The current mid-infrared spectroscopic study is a systematic investigation of hydrated stratum corneum lipid barrier model systems composed of an equimolar mixture of a ceramide, free palmitic acid and cholesterol. Four different ceramide molecules (CER NS, CER NP, CER NP-18:1, CER AS) were investigated with regard to their microstructure arrangement in a stratum corneum lipid barrier model system. Ceramide molecules were chosen from the sphingosine and phytosphingosine groups. The main differences in the used ceramide molecules result from their polar head group architecture as well as hydrocarbon chain properties. The mixing properties with cholesterol and palmitic acid are considered. This is feasible by using perdeuterated palmitic acid and proteated ceramides. Both molecules can be monitored separately, within the same experiment, using mid-infrared spectroscopy; no external label is necessary.
In previous studies, the free radical generating toxin tertiary butylhydroperoxide (t-BuOOH) was found to induce significant cell death in human cortical neuronal cells (HCN2 cells). Pretreatment with the poly (ADP-ribose) polymerase (PARP) inhibitor nicotinamide was able to prevent HCN2 cell death. In this study it is observed that apoptosis is induced following the addition of t-BuOOH at 6 h as indicated by TUNEL-positive cells. When nicotinamide is added prior to t-BuOOH, it is able to prevent neuronal cell death and inhibit apoptosis. DNA microarray studies demonstrate that t-BuOOH administration causes an upregulation of proapoptotic genes like ICH-2 and BimL. On the other hand, nicotinamide-pretreated neurons have higher expression levels of inhibitors of apoptosis (IAP) genes. Therefore, it appears that one mechanism by which nicotinamide acts as neuroprotective agents is by elevating the gene expression levels of IAPs. Moreover, there is an upregulation of the glyceraldehydes-3-phosphate dehydrogenase gene in nicotinamide-pretreated HCN2 cells. Nicotinamide-pretreated cells also had higher expression levels of putative "death domain" genes like p75TNFR, TRAIL2, TNFR1, and HVEM-L. Thus, nicotinamide can regulate multiple apoptotic genes with seemingly opposite roles and through its action on these various genes prevent apoptosis of neuronal cells.
The term cosmeceutical was created over 25 years ago to define products with active substances that cannot be considered cosmetics or drugs. Cosmeceuticals are increasingly popular, with sales representing one of the largest growing segments of the skin care market. These products are found in many forms, including vitamins, peptides, growth factors, and botanical extracts. Cosmeceuticals that contain topically applied vitamins have an increasing role in skin care.
We studied the duration of action and permeability of common analgesics and local anesthetics applied dermally via new carriers--transfersomes--in rats and humans. The therapeutic potential of analgesic transfersomes was evaluated in Sprague-Dawley rats subjected to heat and pressure stimuli. Results were compared with those obtained from administration of lidocaine-containing standard liposomes. In rats, subcutaneous injections of 2% lidocaine solution and of liposomal or transfersomal suspension resulted in a strong initial analgesic effect that decayed within 6-7 min. Characteristic withdrawal time is approximately 30 s. Dermally applied analgesic transfersomes, by contrast, increased heat stimulus reaction to greater than 70 s, 130% longer than in controls that received a placebo or a standard aqueous lidocaine solution. In humans, we tested two groups of nine male and female volunteers, aged between 25 and 60 yr, for pain-suppressing activity assessed by the pinprick method. Each subject received a total of 0.5 mL of a transfersomal preparation containing 7% lidocaine or 4% tetracaine over a forearm area of 9 cm. We conclude that the effectiveness of dermally applied anesthetic transfersomes is similar to that of the corresponding subcutaneous injections of similar drug quantities and that optimally designed transfersomes offer a suitable and promising means for the noninvasive treatment of local pain with direct, topical drug application.
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.
The mechanical parameters, work of fracture, ultimate breaking strength and elongation at fracture, were determined from the stress-strain characteristics of normal human stratum corneum conditioned in various physicochemical environments. These biomechanical properties were found to be highly dependent on the conditioning relative humidity (RH) and solvent extraction history. Over the increasing 0 to 100% RH range, untreated stratum corneum breaking strength decreased 85%, while the work of fracture increased 600%. Elongation at fracture increased from 20% at 0% RH to 190% at 100% RH. Ether extraction increased the magnitude of the breaking strength at all RH's while having little influence on RH dependence of the % elongation at fracture as compared to untreated. Sequential ether-water extraction significantly decreased the fracture elongation at the higher RH's while breaking strengths were less dependent on RH than untreated. The lower extensibility of the ether-water treated samples relative to ether extracted or untreated is consistent with the suggested role of water soluble materials being responsible for the water binding necessary for membrane flexibility. The mechanism for the influence of ether extraction on the breaking strength remains unclear.
The outermost layer of mammalian skin, the stratum corneum, provides the body with a barrier against transepidermal water loss and penetration of agents from outside. The lipid-rich extracellular matrix surrounding the corneocytes in the stratum corneum is mainly responsible for this barrier function. In this study (cryo-) electron diffraction was applied to obtain information about the local lateral lipid organization in the extracellular matrix in relation to depth in human stratum corneum. For this purpose, stratum corneum grid-strips were prepared from native skin in vivo and ex vivo. It was found that the lipid packing in samples prepared at room temperature is predominantly orthorhombic. In samples prepared at 32 degrees C the presence of a hexagonal packing is more pronounced in the outer layers of the stratum corneum. Gradually increasing the specimen temperature from 30 to 40 degrees C induced a further transition from an orthorhombic to a hexagonal sublattice. At 90 degrees C all lipids were present in a fluid phase. These results are in good agreement with previously reported wide angle X-ray diffraction and Fourier transformed infrared spectroscopy studies. We conclude that the lipids in human stratum corneum are highly ordered throughout the stratum corneum and that electron diffraction allows monitoring of the local lipid organization, which contributes to the understanding of stratum corneum barrier function.
The aims of this study were to refine ultradeformable liposomes for oestradiol skin delivery and to evaluate Span 80 and Tween 80 as edge activators compared with sodium cholate. Vesicles containing phosphatidylcholine (PC) mixed with edge activators and oestradiol were prepared. Entrapment efficiency and vesicle size were determined. Interactions between activators and vesicles were investigated using differential scanning calorimetry. Transepidermal permeation of oestradiol from vesicles was studied compared to saturated aqueous control in vitro. The maximum flux (J(max)) and its time (T(max)) were calculated from the flux curves and skin deposition was assessed. The compositions of refined formulations were predicted, liposomes prepared, and tested against control. Entrapment efficiency depended on PC concentration with some contribution from sodium cholate and Tween 80. Vesicle sizes ranged from 124 to 135 nm. Edge activators interacted with lipid bilayers and disrupted packing. The refined edge activator concentrations in PC vesicles were 14.0, 13.3 and 15.5% w/w for sodium cholate, Span 80 and Tween 80, respectively; they increased J(max) by 18, 16 and 15-fold and skin deposition by 8, 7 and 8-fold compared with control. Ultradeformable vesicles thus improved skin delivery of oestradiol compared to control and Span 80 and Tween 80 were equivalent to sodium cholate as edge-activators.
Cutaneous hyperpigmentation occurs in multiple conditions. In addition, many Asian women desire a lighter skin colour. Thus, there is a need for the development of skin lightening agents. Niacinamide is a possible candidate.
To investigate the effects of niacinamide on melanogenesis in vitro and on facial hyperpigmentation and skin colour in vivo in Japanese women.
Melanin production was measured in a purified mushroom tyrosinase assay, cultured melanocytes, a keratinocyte/melanocyte coculture model, and a pigmented reconstructed epidermis (PREP) model. The clinical trials included 18 subjects with hyperpigmentation who used 5% niacinamide moisturizer and vehicle moisturizer in a paired design, and 120 subjects with facial tanning who were assigned to two of three treatments: vehicle, sunscreen and 2% niacinamide + sunscreen. Changes in facial hyperpigmentation and skin colour were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face.
Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes. However, niacinamide gave 35-68% inhibition of melanosome transfer in the coculture model and reduced cutaneous pigmentation in the PREP model. In the clinical studies, niacinamide significantly decreased hyperpigmentation and increased skin lightness compared with vehicle alone after 4 weeks of use.
The data suggest niacinamide is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes.
Novel formulations of the halogenated corticosteroid, triamcinolone-acetonide, based on ultradeformable mixed lipid vesicles, Transfersomes, are described. Their performance was tested in vivo using radioactive label measurements, to study the drug biodistribution, and murine ear edema, to determine the drug bioactivity. Sparse use of drug-loaded Transfersomes on the skin ensures an almost exclusive delivery of triamcinolone-acetonide into the organ, thus arguably increasing the treatment safety. Delivery of triamcinolone-acetonide in the skin with ultradeformable vesicles prolongs the anti-inflammatory drug action several times compared to drug usage in a conventional crème or an ointment, the robustness of biological response for the former being at least identical to the latter. The required dose of Transfersome-based triamcinolone-acetonide is also greatly reduced. The drug dose of 0.2 microg cm(-2) suppresses 75% of arachidonic acid-induced murine ear edema for at least 48 h. In contrast, a conventional formulation of triamcinolone-acetonide requires a 10-fold higher drug dosage to achieve a similar effect. In either case, increasing the applied corticosteroid amount delays the onset of anti-edema action.
This work investigated the effect of electroporation on human epidermal penetration of a model neutral lipophilic compound (estradiol) from saturated aqueous solution and when encapsulated in ultradeformable liposomes. Total amount penetrated and skin deposition were compared with values obtained from passive diffusion. The effect of electrical pulsing on liposome size was investigated. The action of phosphatidylcholine on skin that was structurally altered by such pulses was determined. Electroporation did not affect liposome size. Skin pulsing considerably increased estradiol penetration and skin deposition from solution, relative to passive delivery, with subsequent partial recovery of skin resistance to molecular penetration. Surprisingly, with liposomes, electroporation did not markedly affect estradiol skin penetration. Importantly, liposomal phosphatidylcholine applied during or after pulsing accelerated skin barrier repair, i.e. provided an anti-enhancer or retardant effect.
The isolation of milk fat globule membrane (MFGM) material from buttermilk on a commercial scale has provided a new ingredient rich in phospholipids and sphingolipids. An MFGM-derived phospholipid fraction was used to produce liposomes via a high-pressure homogenizer (Microfluidizer). This technique does not require the use of solvents or detergents, and is suitable for use in the food industry. The liposome dispersion had an average hydrodynamic diameter of 95 nm, with a broad particle-size distribution. Increasing the number of passes through the Microfluidizer, increasing the pressure, or reducing the phospholipid concentration all resulted in a smaller average liposome diameter. Changing these variables did not have a significant effect on the polydispersity of the dispersion. Electron microscopy showed that the dispersions formed had a range of structures, including unilamellar, multilamellar, and multivesicular liposomes. The composition of the MFGM phospholipid material is different from that of the phospholipids usually used for liposome production in the pharmaceutical and cosmetic industries. The MFGM-derived fraction comprises approximately 25% sphingomyelin, and the fatty acids are primarily saturated and monounsaturated. These differences are likely to affect the properties of the liposomes produced from the phospholipid material, and it may be possible to exploit the unique composition of the MFGM phospholipid fraction in the delivery of bioactive ingredients in functional foods.
Beta-sitosterol 3-beta-D-glucoside (Sit-G), an absorption enhancer, was incorporated into ultra-deformable vesicles containing bleomycin to attenuate drug toxicity in human keratinocytes. The presence of Sit-G increased drug entrapment and improved in vitro stability of ultra-deformable vesicles. Confocal laser scanning microscopy revealed the extent to which Sit-G facilitated the penetration of ultra-deformable vesicles containing fluorescent probes into rat skin upon non-occlusive topical application. Furthermore, treatment with preparations incorporating Sit-G resulted in elevated epidermal and dermal concentrations of bleomycin. Ultra-deformable formulation contained Sit-G maintained flexibility for penetration through the skin, increased entrapment efficiency of bleomycin and stability in vitro, and significantly increased distribution of bleomycin in epidermis and dermis compared with those without Sit-G.
Various skin disorders with an inflammatory component often have been treated with steroids and/or oral antibiotics. However, long-term use of these agents has drawbacks: steroids may induce numerous serious side effects such as hypertension, immunosuppression, and osteoporosis, and overuse of oral antibiotics may contribute to the development of bacterial resistance, as well as to a host of nuisance side effects such as diarrhea, yeast infections, and photosensitivity. As a result, alternative oral treatments, such as nicotinamide, have been investigated.
During the past 50 years, many clinical reports have identified nicotinamide as a beneficial agent in the treatment of a variety of inflammatory skin disorders; what's more, its exceptional safety profile at pharmacologic doses makes it a potentially ideal long-term oral therapy for patients with inflammatory skin diseases. A recent large study evaluating nicotinamide for the treatment of acne or rosacea has confirmed the potential benefits of oral nicotinamide as an alternative approach to managing inflammatory lesions associated with acne vulgaris and acne rosacea.
This article reviews the substantial number of reports published over the past 50 years that document the clinical utility and safety of oral and topical formulations of nicotinamide for the treatment of a variety of inflammatory skin conditions.
- Neil Niren MD
UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open
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