Article

Phycocyanin liposomes for topical anti-inflammatory activity: In-vitro in-vivo studies

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Abstract

Objectives: The aim of this work was to investigate the anti-inflammatory activity of C-phycocyanin (C-PC) on skin inflammation after topical administration and the influence of liposomal delivery on its pharmacokinetic properties. Methods: Liposomes of different size and structure were prepared with different techniques using soy phosphatidylcholine and cholesterol. Vesicular dispersions were characterised by transmission electron microscopy, optical and fluorescence microscopy for vesicle formation and morphology, dynamic laser light scattering for size distribution, and Zetasizer for zeta-potential. C-PC skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either free or liposomal drug dispersed in a Carbopol gel. Key findings: The protein was mainly localised in the stratum corneum, while no permeation of C-PC through the whole skin thickness was detected. Two percent C-PC-encapsulating liposomes showed the best drug accumulation in the stratum corneum and the whole skin, higher than that of the corresponding free 2% C-PC gel. Moreover, skin deposition of liposomal C-PC was dose dependent since skin accumulation values increased as the C-PC concentration in liposomes increased. The topical anti-inflammatory activity of samples was evaluated in vivo as inhibition of croton oil-induced or arachidonic acid-induced ear oedema in rats. Conclusions: The results showed that C-PC can be successfully used as an anti-inflammatory drug and that liposomal encapsulation is effective in improving its antiinflammatory activity.

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... SP contains several vital antioxidant and anti-inflammatory compounds as mentioned above, such as chlorophyll, phycocyanin, and carotenoids (β-carotene). The antioxidant and anti-inflammatory properties of phycocyanin have been determined in numerous studies [28, [83][84][85][86][90][91][92][93][94][95][96][97]. Phycocyanin is responsible for reducing oxidative stress and NADPH oxidase [28]. ...
... It scavenges free radicals, such as alkoxy, hydroxyl, and peroxyl radicals, and decreases nitrite production and inducible nitric oxide synthase (iNOS) expression. Phycocyanin also inhibits liver microsomal lipid peroxidation [28, [83][84][85][86][90][91][92][93][94][95][96][97]. ...
... NNRTIs are associated with life-threatening skin reactions and toxic hepatitis [114], these conditions may be ameliorated by SP. Phycocyanin from SP can inhibit liver microsomal lipid peroxidation [28, [83][84][85][86][90][91][92][93][94][95][96][97], and hence reducing toxic hepatitis. Moreso, SP incorporated into skin creams showed promising results as an anti-inflammatory and a wound-healing agent [89]; this can be beneficial in the mitigation of NNRTI-induced skin reactions. ...
Article
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The human immunodeficiency virus (HIV) is one of the most prevalent diseases globally. It is estimated that 37.7 million people are infected with HIV globally, and 8.2 million persons are infected with the virus in South Africa. The highly active antiretroviral therapy (HAART) involves combining various types of antiretroviral drugs that are dependent on the infected person's viral load. HAART helps regulate the viral load and prevents its associated symptoms from progressing into acquired immune deficiency syndrome (AIDS). Despite its success in prolonging HIV-infected patients' lifespans, the use of HAART promotes metabolic syndrome (MetS) through an inflammatory pathway, excess production of reactive oxygen species (ROS), and mitochondrial dysfunction. Interestingly, Spirulina platensis (SP), a blue-green microalgae commonly used as a traditional food by Mexican and African people, has been demonstrated to mitigate MetS by regulating oxidative and inflammatory pathways. SP is also a potent antioxidant that has been shown to exhibit immunological, anticancer, anti-inflammatory, anti-aging, antidiabetic, antibacterial, and antiviral properties. This review is aimed at highlighting the biochemical mechanism of SP with a focus on studies linking SP to the inhibition of HIV, inflammation, and oxidative stress. Further, we propose SP as a potential supplement for HIV-infected persons on lifelong HAART.
... For instance, phycocyanin had anti-inflammatory effect similar to that of non-steroidal drugs and was, thus, effective in decreasing edema index in glucose-oxidase induced inflammation in mouse paw model [141], in carrageenan-induced rat paw edema model (both in intact and adrenalectomized rats) [130], arachidonic acid-and tetradecanoylphorbol acetateinduced ear edema model in mice [130,181,182], and had inhibitory effect in the cotton pellet granuloma test in the rat axilla [130]. Topical administration of phycocyanin containing liposomes resulted in anti-inflammatory activity in croton-oil-induced or arachidonic acid-induced ear edema models in rats [183]. ...
... Similarly, studies showing the high potency of co-administration of phycobiliproteins with low doses of existing anticancer or other drugs may open up new perspectives in the prevention and/or treatment of various diseases. Studies aimed at microencapsulation of phycocyanin [183,257] and phycoerythrin [163] in alginate and chitozan as coating materials [257] and in liposomes [163,183] as well as optimizing its release profile are already going on. This clearly outlines the great interest of the pharmaceutical industry in these compounds. ...
... Similarly, studies showing the high potency of co-administration of phycobiliproteins with low doses of existing anticancer or other drugs may open up new perspectives in the prevention and/or treatment of various diseases. Studies aimed at microencapsulation of phycocyanin [183,257] and phycoerythrin [163] in alginate and chitozan as coating materials [257] and in liposomes [163,183] as well as optimizing its release profile are already going on. This clearly outlines the great interest of the pharmaceutical industry in these compounds. ...
Article
Background: Open tetrapyrroles termed phycobilins represent the major photosynthetic accessory pigments of several cyanobacteria and some eukaryotic algae such as the Glaucophyta, Cryptophyta and Rhodophyta. These pigments are covalently bound to so-called phycobiliproteins which are in general organized into phycobilisomes on the thylakoid membranes. Objective & methods: In this work we first briefly describe the physico-chemical properties, biosynthesis, occurrence, in vivo localization and roles of the phycobilin pigments and the phycobiliproteins. Then the potential applications and uses of these pigments, pigment-protein complexes and related products by the food industry (e.g., as LinaBlue® or the so-called spirulina extract used as coloring food), by the health industry or as fluorescent dyes are critically reviewed. Conclusion: In addition to the stability, bioavailability and safety issues of purified phycobilins and phycobiliproteins, literature data about their antioxidant, anticancer, anti-inflammatory, immunomodulatory, hepatoprotective, nephroprotective and neuroprotective effects, and their potential use in photodynamic therapy (PDT) are also discussed.
... However, only relatively low molecular weight (<500 Da) substances with an adequate lipophilicity can penetrate via passive diffusion into the deeper skin layers or through the skin. Meanwhile, peptides and proteins are poorly absorbed because their molecules are generally large and hydrophilic [55]. ...
... The use of traditional phospholipid vesicles improved the in vivo anti-inflammatory activity depending on the dose. Moreover, the use of liposomes allows to halve the C-PC dose in order to produce the same anti-inflammatory effect as free protein [55]. However, the penetration enhancer-containing vesicles (PEVs), especially propylene glycol, improved the dermal and transdermal delivery of the high molecular weight protein C-PC compared to the conventional liposomes and ethosomes [56]. ...
Article
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Cyano-phycocyanin is one of the active pigments of the blue-green algae and is usually isolated from the filamentous cyanobacteria Arthrospira platensis Gomont (Spirulina). Due to its multiple physiological functions and non-toxicity, cyano-phycocyanin may be a potential substance for the topical treatment of various skin diseases. Considering that the conventional medicine faces drug resistance, insufficient efficacy and side effects, the plant origin compounds can act as an alternative option. Thus, the aim of this paper was to review the wound healing, antimicrobial, antioxidative, anti-inflammatory, antimelanogenic and anticancer properties and mechanisms of cyano-phycocyanin topical activities on human skin. Moreover, possible applications and biotechnological requirements for pharmaceutical forms of cyano-phycocyanin for the treatment of various skin diseases are discussed in this review.
... Phycocyanin has been described as a naturally potent antioxidant (Eriksen, 2008;Kuddus et al., 2013) and anti-inflammatory (Manconia et al., 2009, Mitra et al., 2015 compound. It is evidenced by in vitro and in vivo studies on CPC from Spirulina platensis (Gad et al., 2011). ...
... The stimulatory effect of BPE on healthy bone marrow cells shows its possible role in overcoming the myelosuppression after cancer chemotherapy or radiation therapy (Minkova et al., 2011). Experiments on mice showed that CPC could be successfully used as an anti-inflammatory drug when incorporated in liposomal encapsulation (Manconia et al., 2009). CPC suppressed TNF-α formation and nuclear NF-κB activation when applied to RAW 264.7 macrophages. ...
Chapter
Nutra-cosmeceuticals are a concoction of nutraceutical and cosmeceutical compounds, which is used as oral or topical supplements prepared for marketing, especially for beauty care products. The concept of Nutra-cosmetics with antioxidants has attracted the researchers worldwide. Microalgae are simple, plant-like photosynthetic organisms having the ability to thrive in challenging environmental conditions. Natural colours such as carotenes, xanthophylls, phycocyanin, phycoerythrin, and chlorophyll have a wide range of applications in therapeutics, diagnostics, biomedical research apart from being used as colourants in food and cosmetics. These pigments can be either water or lipid soluble and are invariably produced by microalgae for commercial purposes. The photosynthetic roles of carotenoids, as well as phycobiliproteins from cyanobacteria, have been studied extensively. Additionally, they execute an essential function of protection against light-induced damage by quenching singlet oxygen and superoxide radicals, while carotenoids can be used as a UV absorbing sunscreen. One such Nrf2 activation mechanism makes their role noticeable in photoprotection. This chapter primarily focuses on the role of nutra-cosmeceuticals from microalgae with an emphasis on their potential as sunscreen compounds.
... C-Phycocyanin accumulation in the skin was better with the liposomal gel than the free drug-loaded gel, showing anti-inflammatory activity with the inhibition of edema (60-70%). Myeloperoxidase activity, directly proportional to the neutrophil concentration in the inflamed tissue, was also reduced (60%) [33]. The anti-inflammatory activity of indomethacin-loaded liposomes (PC/CHOL 9/1 mol/mol -Diameter = 200 ± 12 nm -PdI = 0.03) dispersed in xanthan gumbased gel was evaluated in a clinical trial involving 12 healthy human volunteers (aged between 25 and 35 years). ...
... Paclitaxel [59], Cisplatin [60] lipid nanocapsule subcutaneous, intratumoral preclinical (mice) modified gemcitabine [72][73][74] Dendrimer intraperitoneal preclinical (mice) Doxorubicin prodrug [78] Skin disease (severe hemangioma, chronic allergic or atopic dermatis, inflammation, erythema, acne, hidradenitis suppurativa, alopecia, infection, wound healing) liposome transdermal, topical clinical (phase 2) and preclinical (mice, rats, hamsters) Propranolol [22,23], Glycyrrhetic acid [31], Bethamethasone/ Diflucortolone [32], Phycocyanin [33], Indometacin [34], Methylene blue [35,36], Lauric acid [37], VEGF [38], Terbinafine hydrochloride [46] micelle topical preclinical (rats) Dental anesthesia and periapical lesions liposome topical clinical (phase 2) and preclinical (rabbits) Ropivacaine/Benzocaine/Lidocaine [39][40][41][42], Benzocaine [43] polymeric nanoparticle topical preclinical (dogs) ...
Article
The combination of pharmaceutical technologies can be a wise choice for developing innovative therapeutic strategies. The association of nanocarriers and gels provides new therapeutic possibilities due to the combined properties of the two technologies. Gels support the nanocarriers, localize their administration to the target tissue, and sustain their release. In addition to the properties afforded by the gel, nanocarriers can provide additional drug sustained release or different pharmacokinetic and biodistribution profiles than those from nanocarriers administered by the conventional route to improve the drug therapeutic index. This review focuses on recent (over the last ten years) in vivo data showing the advances and advantages of using nanocarrier-loaded gels. Liposomes, micelles, liquid and solid lipid nanocapsules, polymeric nanoparticles, dendrimers, and fullerenes are all nanotechnologies which have been recently assessed for medical applications, such as cancer therapy, the treatment of cutaneous and infectious diseases, anesthesia, the administration of antidepressants, and the treatment of unexpected diseases, such as alopecia.
... The reason being, customary liposomes are less deformable, get dried out totally, fuze and limited to the skin surface [25]. Liposomes don't have capacity to penetrate the phycocyanin into the profound layers of the skin and embodiment productivity of liposomes was found less than 50% [26]. To overcome the destitute penetrability of liposomes through the skin, ethosomes were to begin with created for transdermal conveyance by Elka Touitou. ...
... Recently, it has attracted increasing attention as a potential functional and healthy food [7]. It has been reported that phycocyanin exerts multiple physiological effects, including anti-inflammatory [8,9], antioxidant [10,11], immunomodulatory [12], and anti-bacterial activities [13], among others. In addition, it also shows good antineoplastic values in different cancer cells, such as breast cancer [14,15], ovarian cancer [16], pancreatic cancer [17], colon cancer [18], and malignant melanoma [19], with no side effects on normal tissue cells [7,14]. ...
Article
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Phycocyanin, derived from Spirulina platensis, is a type of natural antineoplastic marine protein. It is known that phycocyanin exerts anticancer effects on non-small-cell lung cancer (NSCLC) cells, but its underlying mechanism has not been elucidated. Herein, the antitumor function and regulatory mechanism of phycocyanin were investigated in three NSCLC cell lines for the first time: H358, H1650, and LTEP-a2. Cell phenotype experiments suggested that phycocyanin could suppress the survival rate, proliferation, colony formation, and migration abilities, as well as induce apoptosis of NSCLC cells. Subsequently, transcriptome analysis revealed that receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was significantly down-regulated by phycocyanin in the LTEP-a2 cell, which was further validated by qRT-PCR and Western blot analysis in two other cell lines. Interestingly, similar to phycocyanin-treated assays, siRNA knockdown of RIPK1 expression also resulted in growth and migration inhibition of NSCLC cells. Moreover, the activity of NF-κB signaling was also suppressed after silencing RIPK1 expression, indicating that phycocyanin exerted anti-proliferative and anti-migratory function through down-regulating RIPK1/NF-κB activity in NSCLC cells. This study proposes a mechanism of action for phycocyanin involving both NSCLC apoptosis and down regulation of NSCLC genes.
... The reason being, conventional liposomes are less deformable, dehydrate completely, fuze and confined to the skin surface [8]. Manconia et al., reported that liposomes do not have ability to permeate the phycocyanin into the deep layers of the skin and encapsulation efficiency of liposomes was found less than 50% [9]. ...
Article
Aim of the present study was to design vesicular gels of etodolac loaded liposomes and ethosomes for effective transdermal delivery. The physicochemical properties of vesicular gels were compared with 45% v/v ethanolic etodolac solution and commercial product (PROXYM®). The liposomes were prepared by film hydration technique whereas ethosomes were prepared by cold method respectively. Both the systems were characterized for various physicochemical properties. The size range of liposomes shows 186 nm–363 nm whereas for ethosomes 170 nm–261 nm respectively. The zeta potential of optimized liposomes and ethosomes was found to be −36.5 mV and −48.3 mV, respectively. The highest %EE of liposomes and ethosomes shows 71.5% and 78.5%, respectively. The permeation of liposomes shows in the range of 67.50%–86.06% whereas ethosomes shows 52.30%–99.49%, respectively. The optimization was done by 3² experimental design. The optimized vesicular dispersions were subjected to gel preparation using carbopol 940 NF. The prepared liposomal gel (ETO-LG) and ethosomal gel (ETO-EG) were optimized and characterized. The vesicular gels showed desirable results compared to other test formulations.
... However, the use of such compounds to prevent skin disorders is limited by both their easy degradation and low bioavailability in vivo. For this reason, many efforts have been devoted to improve the efficacy of bioactive molecules following topical application, and several strategies have been proposed, among which the use of phospholipid vesicles holds great promise (Gillet et al., 2011;Manconi et al., 2009). In particular, liposome-like vesicles, conceptually derived from liposomes, have been developed by modifying the base formulation with supplemental components to obtain effective carriers for topical application (Marianecci et al., 2016). ...
... However, the use of such compounds to prevent skin disorders is limited by both their easy degradation and low bioavailability in vivo. For this reason, many efforts have been devoted to improve the efficacy of bioactive molecules following topical application, and several strategies have been proposed, among which the use of phospholipid vesicles holds great promise (Gillet et al., 2011;Manconi et al., 2009). In particular, liposome-like vesicles, conceptually derived from liposomes, have been developed by modifying the base formulation with supplemental components to obtain effective carriers for topical application (Marianecci et al., 2016). ...
... Because of its excellent spectroscopic property, stability, high absorption coefficient, and high quantum yield, a wide range of promising applications of phycocyanin in biomedical research, diagnostics, and therapeutics has become possible (Jian-Feng, Guang-Ce, Lin, & Zhou, 2007). C-phycocyanin has been suggested to exhibit radical-scavenging activity (Zhou et al., 2005) and to reduce inflammatory responses and oxidative stress (Manconia et al., 2009). This phycobiliprotein also enhances wound healing (Madhyastha, Radha, Nakajima, Omura, & Maruyama, 2008), and acts as a photodynamic agent to eradicate cancer cells in vitro (Li, Chu, Gao, & Li, 2010). ...
Article
PCL with biodegradable property and Spirulina with various biological activities offer good alternative ingredients for the fabrication of functional nanofibers in tissue engineering. The aim of the study is to obtain PCL/Spirulina nanofibers with low diameters and to determine their wettability, antioxidant activity, and phycocyanin release to evaluate their potential as bioactive scaffolds in different applications. PCL/acetic acid/pyridine solutions with three different Spirulina concentrations were electrospun and the obtained nanofibers were investigated. The thinnest PCL/Spirulina nanofibers (117.20 nm) were obtained at 1.5% Spirulina concentration. Although PCL nanofibers with 6% Spirulina concentration showed the highest antioxidant activity and amount of phycocyanin released, PCL nanofibers with 3% Spirulina concentration having similar in vitro results showed superiority when considering the diameter and uniformity of the nanofibers and the cost of the material. The PCL/Spirulina nanofibers with small diameters and antioxidant activity could be regarded as potential extracellular matrix material for tissue engineering.
... [29][30][31][32] Here, we are giving some reference to support above statements. Fadda et al. [36] developed phycocyanin loaded liposomes by film hydration techniques. They reported that phycocyanin (C-Pc) loaded liposomes were adsorbed on stratum corneum and accumulated C-Pc on stratum corneum. ...
Article
Aim: The aim of the present work was to focus on the applicability of liposomes and ethosomes for transdermal delivery. In the current review, we had focused on transdermal delivery by vesicular systems, i.e., liposome and ethosomes, factors affecting their permeation and penetration efficiency, limitations, applications, method of preparations, evaluation parameters, and selection of lipids. In this review, we considered the mechanism of controlled drug release of vesicles by transdermal delivery and the impact of their physicochemical properties. Rheumatoid arthritis (RA) is most frequently suffering disease in the geriatric population. By transdermal delivery, conventional anti-RA (ARA) therapy associated with several disadvantages. The modern ARA therapy; disease-modifying antirheumatic drugs (DMARDs) are more effective in reducing down disease progression. The basic mechanism of action of DMARDs in RA is not clear. The vesicles have a potential role in RA; especially, we focused on the impact of liposomes and ethosomes on RA by transdermal delivery, vesicular mechanism to justification in ARA therapy. Conclusion: The liposomes and ethosomes were beneficial tools for transdermal delivery. They have a potential role to control RA by transdermal delivery.
... C-PC has an anti-inflammatory role in the skin during the tropical administration using liposome carrier for the topical administration of proteins that enhances antiinflammation activity in in vitro and in vivo experiments. It was observed that drug delivery is strongly dependent on vesicle composition and morphology [90]. C-PC exhibited anti-inflammation activity in ear swelling of mouse due to ova albumin by reducing the edema and activity of myeloperoxidase, which is proportional to a number of neutrophils accumulated at inflammation site, is an evidence for antichemoattractant action of biliprotein through LTB4 expression in arachidonic acid mediated ear inflammation in mouse [91]. ...
Article
Background Cancer and other disorders such as inflammation, autoimmune diseases and diabetes are the major health problems observed all over the world. Therefore, identifying a therapeutic target molecule for the treatment of these diseases is urgently needed to benefit public health. C-Phycocyanin (C-PC) is an important light yielding pigment intermittently systematized in the cyanobacterial species along with other algal species. It has numerous applications in the field of biotechnology and drug industry and also possesses antioxidant, anticancer, anti-inflammatory, enhanced immune function, including liver and kidney protection properties. Molecular mechanism of action of C-PC for its anticancer activity could be the blockage of cell cycle progression, inducing apoptosis and autophagy in cancer cells. Objectives The current review summarizes an update on therapeutic applications of C-PC, its mechanism of action and mainly focuses on the recent development in the field of C-PC as a drug that exhibits beneficial effects against various human diseases including cancer and inflammation. Conclusion The data from various studies suggest the therapeutic applications of C-PC such as anti-cancer activity, anti-inflammation, anti-angiogenic activity and healing capacity of certain autoimmune disorders. Mechanism of action of C-PC for its anticancer activity is the blockage of cell cycle progression, inducing apoptosis and autophagy in cancer cells. The future perspective of C-PC is to identify and define the molecular mechanism of its anti-cancer, anti-inflammatory and antioxidant activities, which would shed light on our knowledge on therapeutic applications of C-PC and may contribute significant benefits to global public health.
... In particular, phycocyanin accelerated the wound closure by direct action on fibroblast migration and indirect effect on keratinocyte migration [24]. Unfortunately, its topical therapeutic use is limited by its high molecular weight but, as previously demonstrated, its topical anti-inflammatory activity could be improved by using liposomal formulations [25,26]. Here, the phycocyanin was encapsulated in hyalurosomes, or alternatively in PEG-hyalurosomes, the latter were not used before and were obtained by slightly modifying hyalurosomes, using a mixture of water and polyethylenglycol 400 (PEG400) to dissolve drug and hyaluronan sodium salt. ...
Article
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The phycobiliprotein phycocyanin, extracted from Klamath algae, possesses important biological properties but it is characterized by a low bioavailability due to its high molecular weight. To overcome the bioavailability problems, phycocyanin was successfully encapsulated, using an environmentally-friendly method, into hyalurosomes, a new kind of phospholipid vesicles immobilised with hyaluronan sodium salt by the simple addition of drug/sodium hyaluronate water dispersion to phospholipids. Liposomes were used as a comparison. Vesicles were small in size and homogeneously dispersed, being the mean size always smaller than 150 nm and PI never higher than 0.31. Liposomes were unilamellar and spherical, the addition of the polymer slightly modify the vesicular shape which remain spherical, while the addition of PEG improve the lamellarity of vesicles being multilamellar vesicles. In all cases phycocyanin was encapsulated in good amount especially using hyalurosomes and PEG hyalurosomes (65 and 61 % respectively). In vitro penetration studies suggested that hyalurosomes favoured the phycocyanin deposition in the deeper skin layers probably thanks to their peculiar hyaluronan–phospholipid structure. Moreover, hyalurosomes were highly biocompatible and improved phycocyanin antioxidant activity on stressed human keratinocytes respect to the drug solution. Graphical Abstract
... S. platensis clearly has a protective effect against cell death caused by high fat diet-induced apoptosis. The reactive agents of S. platensis , including β -carotene and phycocyanin, have been reported to have antioxidant and anti-infl ammatory activities and to suppress the expression of iNOS (Gonz á lez et al. 1999, Schafer et al. 2002, Romay et al. 2003, Bai et al. 2005, Cherng et al. 2007, Riss et al. 2007, Katsuura et al. 2009, Manconia et al. 2009, Shih et al. 2009). We found that iNOS expression in the high fat diet groups was strong, while weak staining was observed in the S. platensis treated and control groups. ...
Article
Full-text available
Spirulina platensis is a microalga that may be a source of antioxidants that can reduce body fat deposition. Consumption of a high fat diet produces elevated blood lipid levels, inflammation and apoptosis. We investigated the possible effects of S. platensis on the blood lipid profile, and liver inflammation and apoptosis in rats fed a high fat diet. Sixty-four young male rats were divided into eight equal groups. The control group was fed a basic diet. The experimental groups were fed a diet for 60 days that was prepared by mixing variable amounts of 43% vegetable oil and 10% cholesterol with or without 3% S. platensis mixed with the basal diet. Blood and liver tissue samples were collected from each animal. Serum samples were used to analyze lipid parameters, total antioxidant status and total oxidant status. iNOS and eNOS were determined by immunohistochemistry. TUNEL staining was used to detect apoptosis to investigate a possible connection between inflammation and apoptosis in the liver tissue. The relations between fat deposition and liver degeneration were assessed by Sirius red staining and alpha-smooth muscle actin immunostaining. S. platensis reduced serum HDL-C, LDL-C and triglyceride, increased HDL-C levels in rats fed a high fat diet to near control levels, and reduced iNOS levels and increased eNOS levels in the liver tissue compared to vegetable oil and cholesterol treated groups. The apoptotic index was reduced in the groups that were fed a high fat or a basic diet when supplemented with S. platensis.
... Concerning spirulina, many studies indicated the cyanobacterial proteins in spirulina are the molecules of high potency to work as antioxidants by scavenging peroxyl, hydroxyl, peroxynitrite, superoxide radicals, and as inhibitors of lipid peroxidation (Bhat and Madyastha, 2001). Other studies suggested that spirulina contains several active ingredients, notably phycocyanin and b-carotene that have potent antioxidant and anti-inflammatory activities (Shih et al., 2009;Manconia et al., 2009). ...
Article
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The present study was undertaken to assess the effect of erythropoietin (EPO) and/or spirulina to treat alloxanized-diabetic rats. Eighty male albino rats were equally divided into eight groups; Group I: Normal control rats, Group II: Non-diabetic rats treated with EPO (40 U/kg) injected subcutaneously three times weekly for 3 weeks, Group III: Non-diabetic rats administered orally with spirulina (2 g/kg/d) for 21 days, Group IV: Non-diabetic rats treated by EPO (40 U/kg) together with spirulina (2 g/kg/d) as mentioned in groups II & III, Group V: Alloxanized-diabetic rats. Group VI: Diabetic rats treated with EPO (40 U/kg) as in group II, Group VII: Diabetic rats administered with spirulina (2 g/kg/d) as in group III, Group VIII: Diabetic rats were given with EPO (40 U/kg) and spirulina (2 g/kg/d) as in group IV. Diabetic rat group showed a significant increase in glucose and NO; and a significant decrease in insulin, SOD and CAT levels. Diabetic rats treated with EPO or/and spirulina recorded a significant decrease in the glucose and NO levels; and a significant increase in insulin, SOD and CAT levels when compared with the diabetic group. Histopathologically, diabetic rats treated with EPO or spirulina showed a slight improvement of pancreatic islets and acinar cells, diabetic rats treated with EPO & spirulina together showed an obvious recovery to approximately normal status. IHC, the expression of insulin producing cells (β-cells) of diabetic rats was improved in the three treatment groups with a lesser affinity for EPO than spirulina while with both together showed marked recovery into normal status. In conclusion, all the changes were minimized in spirulina administered group more than EPO group, however, the co-treatment of EPO and spirulina exerted stronger anti-hyperglycemic effects than treatment with each agent alone.
... Two percent C-Phycocyanin liposomes showed drug accumulation higher than that of the corresponding free 2% C-Phycocyanin gel. Liposomal encapsulation also improved its antiinflammatory activity [35]. ...
Article
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Ageing is an inevitable phenomenon. Similar to other organs, skin is also subject to an intrinsic ageing process. Additionally, skin ageing is also influenced by various environmental factors. Existing conventional formulations have limited efficacy because skin serves as a rate limiting barrier for percutaneous absorption of drugs. This has led to the evolution of various novel drug delivery systems. Among these liposomes have received considerable attention due to the numerous advantages they offer. Liposomes, submicroscopic spherical vesicles, were discovered in 1960's. Since then, they have gained popularity as potential carriers for drugs, diagnostics, nutrients, vaccines and other bioactive agents. Liposomes find applications in pharmaceutical, cosmetics and other industrial fields. Various topical actives that have been found to be efficacious in delaying the signs of ageing have been formulated as liposomes resulting in enhanced delivery, biocompatibility, and reduced toxicity. This review focusses on therapeutic use of liposomes in skin ageing.
... Mice were sacrificed after 72 h of treatment (on day 4). The dorsal treated skin area of each mouse was excised and weighted to assess any increase indicative of oedema formation, and immediately stored at −80 • C (De Vry et al., 2005;Manconi et al., 2009b). ...
Article
Diclofenac-loaded phospholipid vesicles, namely conventional liposomes, ethosomes and PEVs (penetration enhancer-containing vesicles) were developed and their efficacy in TPA (phorbol ester) induced skin inflammation was examined. Vesicles were made from a cheap and unpurified mixture of phospho-lipids and diclofenac sodium; Transcutol ® P and propylene glycol were added to obtain PEVs, and ethanol to produce ethosomes. The structure and lamellar organization of the vesicle bilayer were investigated by transmission electron microscopy and small and wide angle X-ray scattering, as well as the main physico-chemical features. The formulations, along with a diclofenac solution and commercial Voltaren Emulgel ® , were tested in a comparative trial for anti-inflammatory efficacy on TPA-treated mice dorsal skin. Vesicles were around 100 nm, negatively charged, able to encapsulate diclofenac in good yields, and disclosed different lamellarity, as a function of the formulation composition. Vesicular formulations promoted drug accumulation and reduced the permeation. Administration of vesicular diclofenac on TPA-inflamed skin resulted in marked attenuation of oedema and leucocyte infiltration, especially using PEVs. Histology confirmed the effectiveness of vesicles, since they provided an amelioration of the tissual damage induced by TPA. The proposed approach based on vesicular nanocarriers may hold promising therapeutic value for treating a variety of inflammatory skin disorders.
... Ear thickness was determined by a digital vernier caliper (Digimatic, Mitutoyo, Japan). Differences in ear thicknesses between treated and untreated areas were used to calculate ear edema inhibition [16]. ...
... Mice were sacrificed after 72 h of treatment (on day 4). The dorsal treated skin area of each mouse was excised and weighted to assess any increase indicative of oedema formation, and immediately stored at −80 • C (De Vry et al., 2005;Manconi et al., 2009b). ...
... Ear thickness was determined by a digital vernier caliper (Digimatic, Mitutoyo, Japan). Differences in ear thicknesses between treated and untreated areas were used to calculate ear edema inhibition [16]. ...
Article
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Melatonin, encapsulated and non-encapsulated, in a topical gel, was comparatively investigated for its in vitro permeation and in vivo anti-inflammatory properties. An average size of the melatonin-encapsulated niosomes of 197 nm with a zeta potential of -78.8 mV and an entrapment efficiency of 92.7% was incorporated into a gel base. In vitro skin permeation of the same gel base incorporated with non-encapsulated melatonin or melatonin niosomes at 5% was comparatively evaluated through porcine skin using Franz diffusion cells and analyzed by spectroflurometry at λex 278 and lem 348 nm. From the same gel base, the permeation rate of non-encapsulated melatonin was about 2.5 times greater than that of melatonin-encapsulated niosomes. In comparison to piroxicam gel and hydrocortisone cream used as the positive controls, topical applications of melatonin and melatonin niosome gels tested in croton oil-induced ear edema in mice suggested that its anti-inflammatory activities were prolonged by the niosomal encapsulation. Similarly, analgesic effect of melatonin was prolonged by niosomal encapsulation using tail flick test in mice. Therefore, its immediate permeation through the skin was retarded by niosomal encapsulation which could also prolong its rapid decline in exerting anti-inflammatory and analgesic activities in vivo.
... According to their findings, the liposomal formulation was an excellent choice for topical formulation containing phycocyanin as an anti-inflammatory agent, and encapsulation could increase the anti-inflammatory effect dose-dependently. Therefore, a lower concentration of liposomal formulation had an impact equal to the higher concentration of free phycocyanin (47). Aisha et al. evaluated the liposomal formulation of Orthosiphon stamineus extracts containing soybean phospholipids. ...
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Objectives: The current study's objectives were to obtain different extracts and essential oils of Symphytum kurdicum and Symphytum asperrimum and to determine the chemical composition, as well as to evaluate free radical scavenging activity (IC50) and minimum bactericidal concentration (MBC), and the effect of liposomal formulation on antimicrobial properties. Materials and methods: Air-dried powdered aerial parts of S. kurdicum and S. asperrimum were used. The antioxidant and antibacterial properties, essential oil compositions, total phenol, and flavonoid contents of different fractions were determined by DPPH test, disk diffusion assay, gas chromatography-mass spectrometry, Folin-ciocalteu reagent, and colorimetric assay method, respectively. The film hydration method was used to fabricate nanoparticles. Results: GC-MS analysis indicated that hexafarnesyl acetone was a major essential oil component. n-butanol and ethyl acetate extracts of S. kurdicum had the highest anti-oxidant activity. Extracts of both plants showed antimicrobial activity. The extracts' maximum inhibition zones against Staphylococcus epidermidis were established. A particle size analyzer detected the formulation size of 140 nm. The optimum formulation of liposomes contains the ratio of 75 mg lecithin, 25 mg cholesterol, and 50 mg herbal extract. Despite the nanoparticles' appropriate particle size, the liposomal extract's antimicrobial effect was lower than that of the free form. Conclusion: Our findings demonstrated that extracts have significant antibacterial and anti-oxidant activities, attributed to their bioactive constituents.
... Spirulina contains sev-eral active ingredients, notably phycocyanin and β-carotene that have potent antioxidant and antiinflammatory activities. C-PC can be successfully used as an anti-inflammatory drug and liposomal encapsulation is effective in improving its anti-inflammatory activity [8]. Phycocyanin has the ability to scavenge free radicals, including alkoxyl, hydroxyl and peroxyl radicals. ...
... In addition, liposomes were highly biocompatible, as demonstrated by the in vitro studies that were carried out while using human keratinocytes. The ability of liposomes to improve the delivery of small and large molecules to the skin is well known [38,39]. Recently, they have been successfully proposed for the skin delivery of phytochemicals due to their high loading and carrier capabilities, as well as affinity with the skin [40]. ...
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Citrus species extracts are well known sources of bio-functional compounds with health-promoting effects. In particular, essential oils are known for their antibacterial activity due to the high content of terpenes. In this work, the steam-distilled essential oil from the leaves of Citrus limon var. pompia was loaded in phospholipid vesicles. The physico-chemical characteristics of the essential oil loaded vesicles were compared with those of vesicles that were loaded with citral, which is one of the most abundant terpenes of Citrus essential oils. The biocompatibility of the vesicles was assessed in vitro in human keratinocytes. Furthermore, the antimicrobial activity of the vesicles was tested while using different bacterial strains and a yeast: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans, respectively. The vesicles were small in size (~140 nm), slightly polydispersed (PI ~0.31), highly negatively charged (~ −73 mV), and able to incorporate high amounts of essential oil or citral (E%~86%). Pompia essential oil and citral exhibited antimicrobial activity against all of the assayed microorganisms, with P. aeruginosa being the least sensitive. Citral was slightly more effective than pompia essential oil against E. coli, S. aureus, and C. albicans. The incorporation of citral in vesicles improved its antifungal activity against C. albicans.
... On the other hand, exposure to oxidative stress has comparatively less effect on PBP content, reducing to the amount from 25 to 60% depending upon types of PBP Munier et al., 2014). A few studies have been conducted on encapsulating the PBP for control release and targeted delivery (Chen et al., 1996;Hu et al., 2008;Manconia et al., 2009;Castangia et al., 2016;Suzery et al., 2017). However, no studies have been reported regarding the stabilization of PBP under the effects of different food processing and storage parameters such as temperature, pH, illumination and oxidative stress. ...
Article
Lipid carriers such as emulsions and liposomes have been widely studied as carriers for different nutraceuticals. However, lipid carriers' physicochemical instability results in the leakage of loaded nutraceuticals and the low solubility into the digestion medium, thus reducing the bioaccessibility. Cellulose nanocrystals (CNC) are nano-sized cellulose derivatives obtained after hydrolysis of cellulosic matrices that possess potential applications in functional foods and nutraceuticals. However, hydrophilicity, anionic surface potential, and poor re-dispersibility limit CNC’s applications. The primary objectives of this research were 1) to modify CNC via adsorbing polyethylene glycol (PEG) to stabilize liposomes and to study its physiochemical stability at different in vitro gastrointestinal tract (GIT) conditions, pH levels (1-11), temperatures (4-100 oC) and illumination periods (4-72 hours); 2) to modify CNC via adsorbing lauric acid to stabilize O/W emulsion and to study its physicochemical stability at different pH (1-11), dilution factors (1-10 times), storage period (up to 30 days) and GIT conditions. Phycobiliprotein and beta-carotene were chosen as model nutraceuticals. In study 1, particle size and microscopic analysis revealed a better physical/kinetic stability for the liposomes stabilized with PEG-adsorbed CNC than the liposomes stabilized with unmodified CNC, resulting in significantly (p≤0.05) smaller average particle size during the initial and mouth phases of the in vitro GIT study, nonetheless a significant (p≤0.05) increase in the particle size from ~300 nm to ~5500 nm at gastric phase due to lower pH. Moreover, stabilized liposomes retained the attributes of phycobiliprotein against pH, illumination, and a temperature of 60 ̊C. In study 2, lauric acid-adsorbed CNC affirmed the kinetic/physical stability of emulsions throughout the GIT phases. Results exhibited a maximum of 65% beta-carotene bioaccessibility for the emulsion stabilized with modified CNC, and 71% for the emulsion stabilized with unmodified CNC. Moreover, a higher amount of lipid oxidation was recorded for the emulsion with stabilized modified CNC than the emulsion stabilized with gum Arabic. Although modified CNC retains the kinetic/physical stability of lipid carriers; however, it increases lipid carriers' chemical instability and decreases the loaded nutraceuticals' bioaccessibility. A strategic modification of CNC is needed to ensure the stability of lipid carriers and increased nutraceuticals bioaccessibility.
... Among nanocarriers, advanced phospholipid vesicles represent an ideal choice when natural and environmentally friendly products must be manufactured, given the natural origin of phospholipids and their easy and low dissipative preparation methods [13]. In particular, they are optimal carriers for skin delivery, which improve the deposition and residence time in the deeper skin layer [14][15][16][17][18]. ...
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In the present study, canthaxanthin was produced by biofermentation from Dietzia natronolimnaea HS-1 (D. natronolimnaea) and was loaded in phospholipid vesicles prepared with natural component using an easy and low dissipative method. Indeed, glycerosomes, hyalurosomes, and glycerohyalurosomes were prepared by direct hydration of both phosphatidylcholine and the biotechnological canthaxanthin, avoiding the use of organic solvents. Vesicles were sized from 63 nm to 87 nm and highly negatively charged. They entrapped a high number of the biomolecules and were stable on storage. Canthaxanthin-loaded vesicles incubated with fibroblasts did not affect their viability, proving to be highly biocompatible and capable of inhibiting the death of fibroblasts stressed with hydrogen peroxide. They reduced the nitric oxide expression in macrophages treated with lipopolysaccharides. Moreover, they favoured the cell migration in an in vitro lesion model. Results confirmed the health-promoting potential of canthaxanthin in skin cells, which is potentiated by its suitable loading in phospholipid vesicles, thus suggesting the possible use of these natural bioformulations in both skin protection and regeneration, thanks to the potent antioxidant, anti-inflammatory and antiageing effects of canthaxanthin.
... Better drug accumulation in the stratum corneum with proven anti-inflammatory activity Manconi et al. (2009) Liposomes in carbopol gel ...
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Dermatological products constitute a big segment of the pharmaceutical market. From conventional products to more advanced ones, a wide variety of dosage forms have been developed till current date. A representative of the advanced delivery means is carrier-based systems, which can load large number of drugs for treatment of dermatological diseases, or simply for cosmeceutical purposes. To make them more favorable for topical delivery, further incorporation of these carriers in a topical vehicle such as gels or creams is made. Therefore in the current review article, an overview is compiled of the most commonly encountered novel carrier based topical delivery systems; namely lipid based (nanoemulsions, microemulsions, solid lipid nanoparticles and nanostructured lipid carriers), and vesicular carriers (non deformable such as liposomes, niosomes, emulsomes and cerosomes, and deformable such as transfersomes, ethosomes, transethosomes and penetration enhancer vesicles), with special emphasis on those loaded in a secondary gel vehicle. A special focus was made on the commonly encountered dermatological diseases, such as bacterial and fungal infections, psoriasis, dermatitis, eczema, vitiligo, oxidative damage, aging, alopecia, and skin cancer.
... Alternatively, it was loaded in solid lipid nanoparticles for the treatment of acne or in nanoemulsions [63,64]. In the present study, the neem oil was loaded in liposomes and hyalurosomes, which were in turn modified by adding argan oil [24,65]. Hyalurosomes, has been selected due their performances as topical carriers for natural bioactives [27]. ...
Article
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Neem oil, a plant-derived product rich in bioactives, has been incorporated in liposomes and hyalurosomes modified by adding argan oil and so called argan-liposomes and argan-hyalurosomes. Argan oil has also been added to the vesicles because of its regenerative and protective effects on skin. In the light of this, vesicles were specifically tailored to protect the skin from oxidative stress and treat lesions. Argan-liposomes were the smallest vesicles (~113 nm); the addition of sodium hyaluronate led to an increase in vesicle size (~143 nm) but it significantly improved vesicle stability during storage. In vitro studies confirmed the free radical scavenging activity of formulations, irrespective of their composition. Moreover, rheological investigation confirmed the higher viscosity of argan-hyalurosomes, which avoid formulation leakage after application. In vitro studies performed by using the most representative cells of the skin (i.e., keratinocytes and fibroblasts) underlined the ability of vesicles, especially argan-liposomes and argan-hyalurosomes, to counteract oxidative stress induced in these cells by using hydrogen peroxide and to improve the proliferation and migration of cells ensuring the more rapid and even complete closure of the wound (scratch assay).
... All rights reserved inhibiting degradation of cytosolic IκB-α and modulating the mitogen-activated protein kinase (MAPK) pathway [48][49][50] . Furthermore, it causes antioxidant effects through scavenging free radicals including alkoxyl, hydroxyl, and peroxyl radicals, suppression of inducible nitric oxide synthase (iNOS) expression, reduction of nitrite production, attenuation of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity as a main source of oxidative stress in adipocytes, and inhibition of liver microsomal lipid peroxidation 48,[51][52][53][54] It is suggested that future robust randomized controlled clinical trials with larger sample size assess the effect of spirulina consumption on inflammation and oxidative stress status of inflammatory disorders including cancers, arthritis, autoimmune diseases, hepatitis, glomerulonephritis, asthma, allergy, and inflammatory bowel disease. Due to the confirmed antioxidant and anti-inflammatory properties of spirulina and also inflammatory nature of mentioned disorders, it could be a more promising interventional therapy in these category of patients. ...
Article
Studies investigating the effects of spirulina on inflammation and oxidative stress status are controversial. Therefore, the current systematic review and meta-analysis aimed to evaluate the impacts of spirulina supplementation on oxidative stress indicators and inflammatory markers. PubMed-Medline, SCOPUS, Web of Science and Embase databases and Google Scholar were searched up to 1 October 2020. Random-effect analysis was applied to perform meta-analysis. Subgroup analyses and multivariate meta-regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration's tool. A total of 11 studies that enrolled 465 subjects were included in our meta-analysis. Pooled results demonstrated a significant increase in IL-2 concentrations (SMD= 2.69 pg/ml; 95% CI: 0.26, 5.11; P=0.03), however this result changed to insignificant (SMD= 0.54 pg/ml; 95% CI: -1.29, 2.27; P> 0.05) when sensitivity analysis performed. A marginal decreasing effect were also found on IL-6 (SMD= -0.72 mg/dl; 95% CI: -1.50, 0.07; P=0.073) and TBARS levels (SMD= -0.65; 95% CI: -1.37, 0.08; P=0.08). In addition, results of subgroup analysis revealed a significant reduction in IL-6 and TBARS concentrations when the baseline BMI of participants was lower than 25 kg/m2 . Moreover, spirulina had no significant effect on TNF-α (SMD= -0.07 mg/dl; 95% CI: -0.33, 0.18; P=0.56) and MDA concentrations (SMD= -0.42; 95% CI: -0.98, 0.14; P=0.14). Spirulina consumption contributed to a significant increase in IL-2 concentrations changing to insignificant after sensitivity analysis and marginal decreasing effects on IL-6 and TBARS levels. No considerable impacts were observed on TNF-α and MDA concentrations.
... On the other hand, exposure to oxidative stress has comparatively less effect on PBP content, reducing to the amount from 25 to 60% depending upon types of PBP Munier et al., 2014). A few studies have been conducted on encapsulating the PBP for control release and targeted delivery (Chen et al., 1996;Hu et al., 2008;Manconia et al., 2009;Castangia et al., 2016;Suzery et al., 2017). However, no studies have been reported regarding the stabilization of PBP under the effects of different food processing and storage parameters such as temperature, pH, illumination and oxidative stress. ...
Thesis
Lipid carriers such as emulsions and liposomes have been widely studied as carriers for different nutraceuticals. However, lipid carriers' physicochemical instability results in the leakage of loaded nutraceuticals and low solubility into the digestion medium, thus reducing the bioaccessibility. Cellulose nanocrystals (CNC) are nano-sized cellulose derivatives obtained after hydrolysis of cellulosic matrices that possess potential applications in functional foods and nutraceuticals. However, hydrophilicity, anionic surface potential, and poor re-dispersibility limit CNC’s applications. The primary objectives of this research were 1) to modify CNC via adsorbing polyethylene glycol (PEG) to stabilize liposomes and to study its physiochemical stability at different in vitro gastrointestinal tract (GIT) conditions, pH levels (1-11), temperatures (4-100 oC) and illumination periods (4-72 hours); 2) to modify CNC via adsorbing lauric acid to stabilize O/W emulsion and to study its physicochemical stability at different pH (1-11), dilution factors (1-10 times), storage period (up to 30 days) and GIT conditions. Phycobiliprotein and beta-carotene were chosen as model nutraceuticals. In study 1, particle size and microscopic analysis revealed a better physical/kinetic stability for the liposomes stabilized with PEG-adsorbed CNC than the liposomes stabilized with unmodified CNC, resulting in significantly (p≤0.05) smaller average particle size during the initial and mouth phases of the in vitro GIT study, nonetheless a significant (p≤0.05) increase in the particle size from ~300 nm to ~5500 nm at gastric phase due to lower pH. Moreover, stabilized liposomes retained the attributes of phycobiliprotein against pH, illumination, and a temperature of 60 ̊C. In study 2, lauric acid-adsorbed CNC affirmed the kinetic/physical stability of emulsions throughout the GIT phases. Results exhibited a maximum of 65% beta-carotene bioaccessibility for the emulsion stabilized with modified CNC, and 71% for the emulsion stabilized with unmodified CNC. Moreover, a higher amount of lipid oxidation was recorded for the emulsion with stabilized modified CNC than the emulsion stabilized with gum Arabic. Although modified CNC retains the kinetic/physical stability of lipid carriers; however, it increases lipid carriers' chemical instability and decreases the loaded nutraceuticals' bioaccessibility. A strategic modification of CNC is needed to ensure the stability of lipid carriers and increased nutraceuticals bioaccessibility.
... A few studies have been conducted on encapsulating the PBP for control release and targeted delivery [10][11][12][13][14]. However, no studies have been reported regarding the stabilization of PBP under the effects of different food processing and storage parameters such as temperature, pH, illumination and oxidative stress. ...
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Stability of phycobiliprotein (PBP), a bioactive protein from Dulse (Palmaria palmata ), to pH, temperature and illumination was improved when loaded within liposomes and encapsulated using polyethylene glycol (PEG) and desulfated cellulose nanocrystals (DCs). Temperature caused complete loss of the fluorescence intensity of PBP at 80 °C, while 60% loss at 60 °C and lower at 4 °C. The losses of fluorescence intensity was observed with PBP loaded liposome (PL), PL with PEG-2000 and PEG 4000, and PL with desulfated CNCs. Extreme pHs (1.0 and 11.0) caused 90 and 30% loss of fluorescence intensity for PBP in solution, whereas 20 and 2% loss was observed for PBP incorporated in the liposomes, respectively. Phycobiliprotein loaded liposomes with desulphated CNCs at PEG 2000 and 4000 mg/L (PLDCs-2000 and PLDCs-4000) were stable to illumination by retaining 70% intensity of PBP when exposed to 72 hours, compared to 15% in solution. Confocal and optical microscopic images confirmed the coalescence of PBP loaded liposome and agglomeration of PLDCs-2000 and PLDCs4000 under acidic pH (<3.0). In contrast, changes in the temperature (4 – 100 °C) and illumination as a function of time up to 72 hours resulted in no change in liposome size and zeta potential.
... Concerning the treatment of cutaneous diseases, the anti-inflammatory potential of phycocyanin-loaded liposomes [213] and the anti-biofilm growth activity of A. platensis fatty acid-loaded coper-alginate nanocarriers [214] were investigated, exhibiting positive effects due to the combination of the bioactives and encapsulation systems. In the first work, liposomes improved phycocyanin accumulation in the whole skin, as well as the anti-inflammatory response, which was confirmed by its superior results when compared to the free phycocyanin gel; while in the second study, the encapsulated fatty acids were able to inhibit half of the film formation with a very low dosage in 24 h. ...
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Microalgae are microorganisms with a singular biochemical composition, including several biologically active compounds with proven pharmacological activities, such as anticancer, antioxidant and anti-inflammatory activities, among others. These properties make microalgae an interesting natural resource to be used as a functional ingredient, as well as in the prevention and treatment of diseases, or cosmetic formulations. Nevertheless, natural bioactives often possess inherent chemical instability and/or poor solubility, which are usually associated with low bioavailability. As such, their industrial potential as a health-promoting substance might be severely compromised. In this context, encapsulation systems are considered as a promising and emerging strategy to overcome these shortcomings due to the presence of a surrounding protective layer. Diverse systems have already been reported in the literature for natural bioactives, where some of them have been successfully applied to microalgae compounds. Therefore, this review focuses on exploring encapsulation systems for microalgae biomass, their extracts, or purified bioactives for food, pharmaceutical, and cosmetic purposes. Moreover, this work also covers the most common encapsulation techniques and types of coating materials used, along with the main findings regarding the beneficial effects of these systems.
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Phycocyanin (PC) is a blue-colored, pigment-protein complex with unique fluorescence characteristics. However, heat leads to PC fading and fluorescence decay, hampering its widespread application. To improve the thermal stability of PC, we induced the in situ mineralization of calcium phosphate (CaP) on the PC surface to prepare PC@Mg-CaP. The nanoparticles were characterized using transmission electron microscopy, energy dispersive spectrometry, fourier transform infrared spectroscopy, and X-ray diffraction. The results showed that PC@Mg-CaP was spherical, and the nanoparticle size was less than 200 nm. The shell of PC@Mg-CaP was composed of amorphous calcium phosphate (ACP). The study suggested that CaP mineralization significantly improved the thermal stability of PC. After heating at 70 °C for 30 min, the relative concentration of PC@Mg-CaP with a Ca/P ratio = 2 was 5.31 times higher than that of PC. Furthermore, the Ca/P ratio was a critical factor for the thermal stability of PC@Mg-CaP. With decreasing Ca/P, the particle size and thermal stability of PC@Mg-CaP significantly increased. This work could provide a feasible approach for the application of PC and other thermal-sensitive biomolecules in functional foods requiring heat treatment.
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This study evaluated the potential neurobehavioral effects of proanthocyanidin-rich-fraction (PRF) obtained from Vitis vinifera seed in male Albino mice. Adult (2½- to 3-month old) male Albino mice were treated with PRF (200, 100, 50 mg/kg) and subjected to diverse behavioral models specially designed for the assessment of central nervous system-acting agents. One-shot intraperitoneal (i.p) injection of PRF (200 and 100 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing, and grooming), anxiety-like responses (% open-arm time, open-arm entries but decreased the total number of enclosed arm times). However, acute i.p administration of PRF decreased the total score of apomorphine-induced stereotyped behaviors, latency to hexobarbitone-induced sleep, and increased the total sleep duration. Moreover, indices of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) were decreased in the PRF treatment groups, especially the PRF (50 mg/kg)-treated mice. Based on these present findings, it could therefore be inferred that systemic administration of PRF of V. vinifera seed origin induces diverse modification on the behaviors of the treated mice stemming from anxiolytic, anticonvulsant, sedative, and decrease in core temperature.
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At present, several drug molecules have been used for the treatment of rheumatoid arthritis (RA). However, the utilization of these compounds through the oral and parenteral route is limited due to low bioavailability, rapid metabolism, poor absorption, first-pass effect, and serious adverse effects. A transdermal delivery system is an appealing option in this scenario, as it possesses the proficiency to overcome drawbacks associated with the oral and parenteral route. With the innovation of several enhancement strategies, many therapeutic agents have been administered transdermally, proposing an exceptional approach to treat RA. The present article provides an insight into the etiology and pathophysiology of RA. The challenges of the transdermal route and the strategies to improve those problems are described. The current advances in increasing the transdermal efficiency of the therapeutics against RA are discussed. Limitations and advantages regarding the state of the art transdermal delivery system and future outlook are also summarized.
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This study describes the physicochemical properties of soybean asolectin (ASO) liposomes loaded with phycocyanin (Phy) extracted from Spirulina sp. LEB 18. The effects of Phy in the liposomes´ properties were investigated by Fourier transform infrared spectroscopy (FTIR), ¹H and ³¹P nuclear magnetic resonance (NMR), zeta (ζ)-potential, dynamic light scattering (DLS) and ultraviolet-visible (UV-vis) techniques. Phy restricted the motion of ASO polar and interface groups and disrupted the package arrangement of the lipid hydrophobic regions, as a likely effect of dipolar and π interactions related to its amino acid residues and pyrrole portions. These interactions were correlated to antiradical/antioxidant Phy responses obtained by 2,2-diphenyl-1-picrylhidrazil (DPPH) assay, thiobarbituric acid reactive substances (TBARS) and ferric reducing antioxidant power (FRAP) methods, and discussed to bring new chemical perspectives about Phy-loaded liposomes-related nutraceutical applications in inflammatory and viral infection processes.
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Interest in the nutritional value and pharmacological activities of blue-green algae has gradually increased. Spirulina extracts show protective effects against apoptosis and inflammatory damage in various cell types. Here, we investigated the protective effects of extracts from Spirulina maxima in a cytokine-mediated type 1 diabetes model in vitro and in streptozotocin-induced diabetic Wistar rats in vivo. Interleukin-1β and interferon-gamma induced substantial cytotoxicity to RINm5F rat insulinoma cells, increasing nitric oxide (NO) production, nuclear factor-kappa B (NF-κB) activity, the expression of endoplasmic reticulum (ER) stress genes, and activation of mitogen-activated protein kinases and key genes related apoptosis. However, the cytotoxicity of cytokines was significantly attenuated by Spirulina extract, which effectively prevented NO production by inhibiting the synthesis of cytokine-activated NO synthase (iNOS), and apoptosis was suppressed. These results suggest that Spirulina extract might be effective to preserve the viability and function of pancreatic β-cells against cytotoxic conditions. Moreover, diabetic mice orally administered Spirulina extract showed decreased glucose levels, increased insulin, and improvement in liver enzyme markers. The antioxidant effect of Spirulina extract may be helpful in treating type 1 diabetes by enhancing the survival, and reducing or delaying cytokine-mediated β-cells destruction.
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Phycocyanin (Pc) is one of the active pigment constituents ofSpirulinamicroalgae. It has been used for its potent antioxidant and anti-inflammatory properties. However, the protective effects of Pc against ultraviolet-B (UVB)-induced primary skin cells damage are still undefined. In the present study, we investigated whether Pc prevented UVB-induced apoptotic cell death in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Pc induced the transcription of heme oxygenase-1 (HO-1). Furthermore, Pc treatments resulted in a marked increase in nuclear factor erythroid-derived 2 (NF-E2)-like 2 (Nrf-2) nuclear translocation. Also, Pc protected UVB induced apoptosis and reduced the p53 and Bax levels, as well as caspase-3 activation. Pc treatment showed a significantly enhanced effect on the phosphorylation of protein kinase C (PKC) α/β II, but not that of p38 mitogen-activated protein kinase (MAPK) or Akt. Induction of HO-1 induced by Pc was suppressed by Go6976, a selective inhibitor of PKC α/β II. In addition, knockdown of HO-1 by small interfering (siRNA) caused a significant increase in poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and caspase-3 activation after Pc pretreatment. Taken together, our results demonstrate that Pc-induced expression of HO-1 is mediated by the PKC α/β II-Nrf-2/HO-1 pathway, and inhibits UVB-induced apoptotic cell death in primary skin cells.
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Liposomes are spherical vesicles consisting of one or more concentric phospholipid bilayers enclosing an aqueous core. Being both nontoxic and biodegradable, liposomes represent a powerful delivery system for several drugs. They have improved the therapeutic efficacy of drugs through stabilizing compounds, overcoming obstacles to cellular and tissue uptake and increasing drug biodistribution to target sites in vivo, while minimizing systemic toxicity. This review offers an overview of liposomes, thought the exploration of their key fundamentals. Initially, the main design aspects to obtain a successful liposomal formulation were addressed, following the techniques for liposome production and drug loading. Before application, liposomes required an extensive characterization to assurance in vitro and in vivo performance. Thus, several properties to characterize liposomes were explored, such as size, polydispersity index, zeta potential, shape, lamellarity, phase behavior, encapsulation efficiency, and in vitro drug release. Topics related with liposomal functionalization and effective targeting strategies were also addressed, as well as stability and some limitations of liposomes. Finally, this review intends to explore the current market liposomes used as a drug delivery system in different therapeutic applications.
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Une nouvelle plateforme hydrogel uniquement formée par l’association de nanocapsules lipidiques (NCLs) a été développée en s’inspirant de précédents travaux utilisant une gemcitabine modifiée. Afin de limiter la toxicité de l’hydrogel, la gemcitabine a été remplacée par la cytidine, rendue amphiphile par une chaîne aliphatique (Cyt-C16). Placée à l’interface huile/eau des NCLs, la Cyt-C16 permet la formation d’un réseau tridimensionnel de NCLs à l’origine de la gélification. Un plan de mélange a permis d’optimiser les procédés de formulation de 4 tailles de NCLs modèles. Les propriétés viscoélastiques des hydrogels sont modulables. Plus les concentrations en NCLs et Cyt-C16 sont élevées, plus le gel est « rigide », indépendamment de la taille des NCLs qui doit être supérieure à 50 nm pour permettre la gélification. Les hydrogels sont injectables et permettent une libération prolongée de NCLs (de taille mono-disperse), sans toxicité supplémentaire in vitro, du fait de la présence de la Cyt-C16. De plus, uniquement solubilisée dans l’huile,la Cyt-C16 permet d’obtenir un organogel, dont les propriétés viscoélastiques sont renforcées en augmentant sa concentration. L’injection sous-cutanée (SC) in vivo des deux gels est bien tolérée et entraine une réaction inflammatoire locale comparable à celle provoquée par un excipient pharmaceutiquement acceptable. Ces deux formes pourront être utilisées pour libérer de façon prolongée différents actifs. Deux applications précliniques des hydrogels ont été explorées, l’une utilisant la voie SC pour cibler les ganglions lymphatiques, la seconde permettant un traitement local des suites opératoires d’une résection de glioblastome.
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Phycobiliproteins are brilliantly colored, highly fluorescent components of the photosynthetic light-harvesting antenna complexes of cyanobacteria (blue-green algae), red algae and cryptomonads. These proteins carry covalently attached linear tetrapyrrole pigments related structurally to biliverdin. Phycobiliproteins, purified from certain organisms, are isolated as either trimers, ()3, of approximatelyM r 110–120103 (e.g., allophycocyanins), or hexamers, ()6, of aboutM r 250103 (certain phycoerythrins). Three phycobiliproteins R-phycoerythrin, B-phycoerythrin, and allophycocyanin serve as valuable fluorescent tags with numerous applications in flow cytometry, fluorescence activated cell sorting, histochemistry and, to a limited degree, in immunoassay and detection of reactive oxygen species. These applications exploit the unique physical and spectroscopic properties of phycobiliproteins.
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This study was performed to establish a useful method for monitoring the effects of inhibitors of 5-lipoxygenase (5-LO) and/or cyclooxygenase (CO) and for differential evaluation of these inhibitors. After oral dosing, CO inhibitors such as indomethacin (20-40 mg/kg) and ketoprofen (40-80 mg/kg), zileuton (5-LO inhibitor, 20-80 mg/kg) and MK886 (5-LO-activating-protein inhibitor, 640 mg/kg) potently suppressed arachidonic acid (AA, 0.25 mg)-induced ear edema in mice. Methysergide (serotonin antagonist, 20 mg/kg) showed a slight anti-edematous effect, while mepyramine (160 mg/kg) and bromelain (320 mg/kg) had no effect. The anti-edematous effects of indomethacin and ketoprofen were reduced by concomitant topical application of prostaglandin E2 (PGE2, 1 micrograms/ear), but not by concomitant intradermal application of leukotriene C4 (LTC4, 0.1 micrograms/ear). On the contrary, the anti-edematous effects of zileuton and MK886 were reduced by LTC4, but not by PGE2. Dual (5-LO and CO) inhibitors such as phenidone (80-160 mg/kg) and BW755C (40-80 mg/kg), which inhibited the biosynthesis of LTB4 13-15 times more potently than that of PGE2 in rat peritoneal exudate cells, also showed anti-edematous effects that were reduced by LTC4, but not by PGE2. These results suggest that the AA (0.25 mg)-induced ear edema in mice is mainly mediated by LTs and PGs and is suitable for evaluating inhibitors of 5-LO and/or CO, and that an application of LTC4 or PGE2 with AA is a useful method for differential evaluation of these inhibitors.
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Phycocyanin is a pigment found in blue-green algae which contains open chain tetrapyrroles with possible scavenging properties. We have studied its antioxidant properties. Phycocyanin was evaluated as a putative antioxidant in vitro by using: a) luminol-enhanced chemiluminescence (LCL) generated by three different radical species (O2-, OH., RO.) and by zymosan activated human polymorphonuclear leukocytes (PMNLs), b) deoxyribose assay and c) inhibition of liver microsomal lipid peroxidation induced by Fe+2-ascorbic acid. The antioxidant activity was also assayed in vivo in glucose oxidase (GO)-induced inflammation in mouse paw. The results indicated that phycocyanin is able to scavenge OH. (IC50 = 0.91 mg/mL) and RO. (IC50 = 76 microg/mL) radicals, with activity equivalent to 0.125 mg/mL of dimethyl sulphoxide (DMSO) and 0.038 microg/mL of trolox, specific scavengers of those radicals respectively. In the deoxyribose assay the second-order rate constant was 3.56 x 10(11) M(-1) S(-1), similar to that obtained for some non-steroidal anti-inflammatory drugs. Phycocyanin also inhibits liver microsomal lipid peroxidation (IC50 = 12 mg/mL), the CL response of PMNLs (p < 0.05) as well as the edema index in GO-induced inflammation in mouse paw (p < 0.05). To our knowledge this is the first report of the antioxidant and anti-inflammatory properties of c-phycocyanin.
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Two New Age foods which contain high concentrations of whole food nutrients are the single-celled microalgae Chlorella and Spirulina. They are accepted as functional foods, which are defined as products derived from natural sources, whose consumption is likely to benefit human health and enhance performance. These foods are used as a supplement/ingredient or as a complete food to enhance the performance and state of the human body, or improve a specific bodily function. Functional foods are used mainly as products to nourish the human body after physical exertion or as a preventive measure against ailments. We determined the fatty acid compositions, particularly polyunsaturated fatty acid compositions, of Chlorella and Spirulina by capillary column-gas chromatography. The data obtained show that Spirulina contains unusually high levels of gamma-linolenic acid, an essential polyunsaturated fatty acid.
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Noninvasive transdermal insulin delivery could provide diabetic patients with sustained physiological levels of basal insulin in a pain-free manner. We have developed a novel transdermal lipid-based system (Biphasix) suitable for macromolecule delivery across the skin. The objective of this study was to evaluate the pharmacological effects of the Biphasix-insulin delivery system in a diabetic rat model. Transdermal patches (one per animal) containing Biphasix-insulin formulation (10 mg of recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 48 h. Blood glucose was monitored every 2-4 h using a Lifescan glucose meter. Serum insulin levels were analysed by enzyme-linked immunosorbent assay. A decrease in blood glucose of 43.7 +/- 3.8% (mean +/- SEM, n = 25) was observed compared with initial blood glucose levels. The duration of the response was 51.5 +/- 3.7 h (mean +/- SEM, n = 25). Serum insulin after application of the transdermal Biphasix-insulin patch was 20.08 +/- 5.44 micro IU/mL (mean +/- SEM, n = 13) during the steady state, which was not statistically different from the insulin levels obtained 2 h after subcutaneous injection of 1 mg of recombinant human insulin solution. Insulin bioavailability from the transdermal Biphasix-insulin patches was 21.5 +/- 6.9% (mean +/- SEM, n = 13) based on serum insulin and 39.5 +/- 8.5% (mean +/- SEM, n = 25) based on the pharmacodynamic blood glucose-lowering effects. The Biphasix system successfully delivered insulin transdermally, as evidenced by a significant sustained decrease in blood glucose in diabetic rats, with a corresponding increase in serum insulin. These results support the feasibility of developing a transdermal insulin patch for human applications.
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Phycocyanin (Pc) is a phycobiliprotein that has been recently reported to exhibit a variety of pharmacological properties. In this regard, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective effects have been experimentally attributed to Pc. When it was evaluated as an antioxidant in vitro, it was able to scavenge alkoxyl, hydroxyl and peroxyl radicals and to react with peroxinitrite (ONOO(-);) and hypochlorous acid (HOCl). Pc also inhibits microsomal lipid peroxidation induced by Fe(+2)-ascorbic acid or the free radical initiator 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Furthermore, it reduces carbon tetrachloride (CCl(4))-induced lipid peroxidation in vivo. Pc has been evaluated in twelve experimental models of inflammation and exerted anti-inflammatory effects in a dose-dependent fashion in all of these. Thus, Pc reduced edema, histamine (Hi) release, myeloperoxidase (MPO) activity and the levels of prostaglandin (PGE(2)) and leukotriene (LTB(4)) in the inflamed tissues. These anti-inflammatory effects of Pc can be due to its scavenging properties toward oxygen reactive species (ROS) and its inhibitory effects on cyclooxygenase 2 (COX-2) activity and on Hi release from mast cells. Pc also reduced the levels of tumor necrosis factor (TNF-alpha) in the blood serum of mice treated with endotoxin and it showed neuroprotective effects in rat cerebellar granule cell cultures and in kainate-induced brain injury in rats.
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Advances in molecular biology have given us a wide range of protein and peptide-based drugs that are unsuitable for oral delivery because of their high degree of first-pass metabolism. Though parenteral delivery is the obvious answer, for the successful development of commercial chronic and self-administration usage formulations it is not the ideal choice. Transdermal delivery is emerging as the biggest application target for these agents, however, the skin is extremely efficient at keeping out such large molecular weight compounds and therapeutic levels are never going to be realistically achieved by passive absorption. Physical enhancement mechanisms including: iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles and jet-propelled particles are emerging as solutions to this topical delivery dilemma. Adding proteins and peptides to the list of other large molecular weight drugs with insufficient passive transdermal fluxes to be therapeutically useful, we have a collection of pharmacological agents waiting for efficient delivery methods to be introduced. This article reviews the current state of physical transdermal delivery technology, assesses the pros and cons of each technique and summarises the evidence-base of their drug delivery capabilities.
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The aim of this work was to formulate minoxidil loaded liposome and niosome formulations to improve skin drug delivery. Multilamellar liposomes were prepared using soy phosphatidylcholine at different purity degrees (Phospholipon 90, 90% purity, soy lecithin (SL), 75% purity) and cholesterol (Chol), whereas niosomes were made with two different commercial mixtures of alkylpolyglucoside (APG) surfactants (Oramix NS10, Oramix CG110), Chol and dicetylphosphate. Minoxidil skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either drug vesicular systems or propylene glycol-water-ethanol solution (control). Penetration of minoxidil in epidermal and dermal layers was greater with liposomes than with niosomal formulations and the control solution. These differences might be attributed to the smaller size and the greater potential targeting to skin and skin appendages of liposomal carriers, which enhanced globally the skin drug delivery. The greatest skin accumulation was always obtained with non-dialysed vesicular formulations. No permeation of minoxidil through the whole skin thickness was detected in the present study irrespective of the existence of hair follicles. Alcohol-free liposomal formulations would constitute a promising approach for the topical delivery of minoxidil in hair loss treatment.
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Wound repair requires both recruitment and well co-ordinated actions of many cell types including inflammatory cells, endothelial cells, epithelial cells and importantly fibroblast cells. Urokinase-type plasminogen activator (uPA) system plays a vital role in wound healing phenomenon. We have previously demonstrated that C-phycocyanin (C-pc), a biliprotein from blue-green algae, transcriptionally regulates uPA through cAMP-dependent protein kinase A (PKA) pathway. To date, a role for C-pc in wound-healing scenario is not elucidated. This study was designed to examine the wound-healing property of C-pc in relation to fibroblast proliferation and migration. C-pc increased fibroblast proliferation in a dose-dependent manner. It also enhanced G1 phase of cell cycle and increased the expressions of cyclin-dependent kinases 1 and 2, which facilitate cell cycle progression, in a uPA-independent manner. In vitro wound healing and migration assays revealed the pro-migratory properties of C-pc. Short-interference RNA studies demonstrated that uPA was necessary for C-pc-induced fibroblast migration. C-pc also significantly elevated the expressions of chemokines (MDC, RANTES, Eotaxin, GRO alpha, ENA78 and TARC) and Rho-GTPases (Cdc 42 and Rac 1) in a uPA-dependent manner. Pre-treatment of C-pc-stimulated cells with pharmacological inhibitor of PI-3K (LY294002) annulled the expression of GTPases implying that Rac 1 and Cdc 42 were induced through PI-3K pathway. C-pc-induced cellular migration towards wounded area was also negatively affected by PI-3K inhibition. In vivo wound-healing experiments in mice validated our finding that C-pc accelerates wound healing. Our data provides conclusive evidence of a novel therapeutic usage for C-pc as a wound-healing agent. C-pc is a food and drug administration (FDA)-approved health supplement. We believe this compound can also be beneficial in healing of internal wounds, such as ulcers.
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Two New Age foods which contain high concentrations of whole food nutrients are the single-celled microalgae Chlorella and Spirulina. They are accepted as functional foods, which are defined as products derived from natural sources, whose consumption is likely to benefit human health and enhance performance. These foods are used as a supplement/ingredient or as a complete food to enhance the performance and state of the human body, or improve a specific bodily function. Functional foods are used mainly as products to nourish the human body after physical exertion or as a preventive measure against ailments. We determined the fatty acid compositions, particularly polyunsaturated fatty acid compositions, of Chlorella and Spirulina by capillary column-gas chromatography. The data obtained show that Spirulina contains unusually high levels of gamma-linolenic acid, an essential polyunsaturated fatty acid.
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This work describes the preparation, characterization and properties of niosomal and liposomal carriers for the topical application of 8-methoxypsoralen (8-MOP). Large multilamellar (MLV) and sonicated unilamellar (UV) vesicular systems were prepared from either non-ionic surfactant octyl/decyl polyglucoside (Oramix CG110) or hydrogenated soy phosphatidylcholine (Phospholipon 90H), cholesterol and a positive or negative charge inducer. The formulations were characterized using transmission electron microscopy (TEM) and Cryo-TEM, dynamic light scattering, incorporation efficiency and diffusion experiments through a silicone membrane. The effects of the vesicular incorporation on the 8-MOP diffusion through and into the skin were investigated in vitro using newborn pig skin. Statistical analysis of the data showed that all the vesicular carriers increased the total 8-MOP permeation through the skin when compared to a control hydroalcoholic solution. Moreover, the amount of drug delivered into the skin was affected by the size and surface charge of the vesicles. Indeed, sonicated, positively charged octyl/decyl polyglucoside niosomes showed the greatest accumulation of 8-MOP in the skin (epidermis and dermis). These results suggest that our niosomes and liposomes may be suitable carriers in an 8-MOP cutaneous target.
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In dermal and transdermal delivery, the skin is used as a portal of entry for drugs, for localized and systemic treatment. Because of the barrier properties of the outer layer of the skin, in many cases, permeation-enhancing agents are needed to achieve therapeutic levels of drug. Classic liposomal systems were found to be effective at forming drug reservoir in the upper layers of the skin, for local skin therapy. Recently, it was found that ethosomal carriers, phospholipid vesicular systems containing relatively high concentrations of alcohol, were very effective at enhancing dermal and transdermal delivery of both lipophilic and hydrophilic molecules. Fluorescent probes delivered from ethosomal systems reached the deep strata of the skin. Delivery of minoxidil to the pilosebaceous units from ethosomes was much greater compared to delivery from classic liposomes. In addition, clinical studies with aciclovir showed that ethosomal formulations were superior to the currently available topical therapy at treating recurrent herpes labialis. Ethosomal systems were also highly effective at transdermal delivery of drugs. In vivo skin permeation of testosterone from patches containing ethosomal drug were more effective at delivering testosterone through rabbit pinna skin than commercially available Testoderm patches. Results using trihexyphenidyl hydrochloride ethosomes indicated that this system has the potential to be further developed into an antiparkinsonian patch. Lastly, the transdermal delivery of insulin from an ethosomal carrier resulted in lower blood glucose levels in normal and diabetic rats in vivo, with a plateau effect lasting for at least 8 h. Drug Dev. Res. 50:406–415, 2000. © 2000 Wiley-Liss, Inc.
Article
Abstract In a previous report (1), we showed that the rate and extent of uptake of cyclosporin-A (CsA) following topical application of nonionic liposomal formulations composed of glyceryl dilaurate (GDL), cholesterol (CH), and polyoxyethylene-10-stearyl ether (POE-10) into and through hairless mouse skin mounted on Franz diffusion cells could be controlled by varying the ratios of GDL to POE-10 (CH being held constant at 15 wt%). However, the pathways of transport as well as the dominant factors that control drug delivery from these formulations are not well understood. In this report, we describe results from studies similar in design to that reported earlier but using the melted form of the lipid components as a vehicle for transport of CsA into and through hairless mouse skin. The results suggest that the transport of CsA from liposomal formulations into and through the skin occurs as a result of dehydration of the liposomes followed by melting of the lipid components on the skin. Microautoradiographic studies suggest that CsA is predominantly transported via the pilosebaceous pathway.
Article
Recently, a large number of new and potentially potent peptide and protein drugs have been developed. Their systemic delivery is difficult because they are rapidly cleared from the bloodstream, are of large molecular size, are vulnerable to proteolytic attack and tend to undergo aggregation, adsorption and denaturation. Controlled release strategies have many advantages over the current delivery method of injection or intervenous infusion. Controlled release allows for prolonged delivery while maintaining the drug concentration within therapeutic limits. It also improves and increases patient compliance by removing the discomfort of repeated applications. The transdermal route of delivery is particularly attractive because it avoids peptide and protein degradation via the gastrointestinal tract and the hepatic first-pass effect, and delivery can be interrupted by simply removing the device. Its primary problem is that the skin is an excellent barrier to large, hydrophilic, polar compounds. Recent work in the area of transdermal peptide and protein drug delivery is overviewed, including strategies such as prodrugs, chemical enhancement, iontophoresis, electroporation, and ultrasound, with focus on mass-transport mechanisms of different systems. Of the strategies studied, iontophoretic delivery appears the most promising. It is clear, however that more work remains to be done before transdermalpeptide and protein delivery devices come to market. Chemical engineers can contribute significantly to further research in this exciting area.
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A critical analysis of (trans) dermal delivery of substances encapsulated within liposomes and niosomes is presented. Topical liposomes or niosomes may serve as solubilization matrix, as a local depot for sustained release of dermally active compounds, as penetration enhancers, or as rate-limiting membrane barrier for the modulation of systemic absorption of drugs. The mechanism(s) of vesicle-skin interaction and drug delivery are being extensively investigated using radioactive- or fluorescence-labeled marker molecules and drugs, and various electron and (laser) light microscopic visualization techniques, and different models describing the interaction with and fate of vesicles in the skin have been proposed. With the current experimental data base on hand, most investigators agree that direct contact between vesicles and skin is essential for efficient delivery, although phospholipids per se apparently do not penetrate into deeper skin layers. Investigators have mostly focused on dermal corticosteroid liposome products. However, localized effects of liposome-associated proteins such as superoxide dismutase, tissue growth factors and interferons appear also to be enhanced. The delivery of liposome-encapsulated proteins and enzymes into deeper skin layers has been reported, although the mechanism of delivery remains to be elucidated. An objective assessment of the performance of topical liposome formulations vs. conventional dosage forms is frequently obscured by investigators comparing equal concentrations, rather than equivalent thermodynamic activities of their respective formulations. We conclude that liposomes and niosomes may become a useful dosage form for a variety of dermally active compounds, specifically due to their ability to modulate drug transfer and serve as nontoxic penetration enhancers.
Article
New vehicles for the non-invasive delivery of agents are introduced. These carriers can transport pharmacological agents, including large polypeptides, through the permeability barriers, such as the intact skin. This capability depends on the self-regulating carrier deformability which exceeds that of the related but not optimized lipid aggregates by several orders of magnitude. Conventional lipid suspensions, such as standard liposomes or mixed lipid micelles, do not mediate a systemic biological effect upon epicutaneous applications. In contrast to this, the properly devised adaptable carriers, when administered on the intact skin, transport therapeutic amounts of biogenic molecules into the body. This process can be nearly as efficient as an injection needle, as seen from the results of experiments in mice and humans with the insulin-carrying vesicles. The carrier-mediated transcutaneous insulin delivery is unlikely to involve shunts, lesions or other types of skin damage. Rather than this, insulin is inferred to be transported into the body between the intact skin cells with a bio-efficiency of at least 50% of the s.c. dose action.
Article
A novel method of liposome preparation has been developed which is simple to use, employs mild conditions and is capable of efficient entrapment of a wide range of materials. Conditions have been established to allow optimum levels of entrapment; typically 40–50% for the protocols used here, though this can be increased by using additional lipid. The procedure is based on induction of fusion of preformed vesicles by means of dehydration and controlled rehydration. Preliminary evidence suggests that the liposomes are primarily oligo and multilamellar. Scale-up of the procedure for industrial use is expected to be straightforward.
Article
We have found that mouse ear oedema induced by the topical application of arachidonic acid is not a specific screen for compounds inhibiting the lipoxygenase or cyclo-oxygenase pathways of arachidonic acid metabolism. Although such compounds are able to reduce the oedema substantially, pharmacological agents such as histamine antagonists, phosphodiesterase inhibitors, free radical scavengers, and also various compounds not normally considered to have anti-inflammatory properties, can equally effectively reduce the oedema. A mutual potentiation of the effects of prostaglandins, leukotrienes and mast cell-derived histamine would allow many, but not all, of the active agents to be rationalised. The ability of compounds not influencing these three types of inflammatory mediators to reduce the oedematous response means the model is of limited value for directed screening.
Article
The temporal patterns of edema and accumulation of the PMN marker enzyme, myeloperoxidase (MPO), were examined following application of tetradecanoylphorbol acetate (TPA) to mouse ears. After application of 2.5 micrograms TPA, edema peaked at 6 hr, while MPO activity peaked at 24 hr. Pharmacological agents with defined mechanisms of action, delivered orally or topically, were assessed for effects on these responses. For oral administration, compounds were delivered 1 hr before and 6 hr after TPA and for topical administration compounds were delivered at 15 min and 6 hr after TPA. Topical and oral corticosteroids inhibited both edema and MPO accumulation. Cyclooxygenase and lipoxygenase inhibitors were very effective against MPO accumulation but were either inactive or moderately active vs edema. Anti-histamine/anti-serotonin agents had little effect on edema, but could inhibit or exacerbate MPO accumulation depending on dose and route of administration. Topically applied histamine itself did not effect TPA-induced edema, but markedly suppressed MPO accumulation. Acetone, the vehicle, when topically applied between 0.5 and 2 hr after TPA inhibited MPO accumulation by 60-80%, but had little effect on edema. Acetone applied before 0.5 hr or after 2 hr had no effect on either parameter. These results indicate that in the TPA-induced ear inflammation model the MPO response at 24 hr may be a useful additional indicator of drug activity.
Article
The topical delivery of liposomally encapsulated interferon was evaluated in the cutaneous herpes simplex virus guinea pig model. Application of liposomally entrapped interferon caused a reduction of lesion scores, whereas application of interferon formulated as a solution or as an emulsion was ineffective. The method of liposomal preparation rather than the lipid composition of the bilayers appeared to be the most important factor for reducing lesion scores. Only liposomes prepared by the dehydration-rehydration method were effective. This finding implied that the dehydration and subsequent rehydration of the liposomes facilitate partitioning of the interferon into liposomal bilayers, where the drug is positioned for transfer into the lipid compartment of the stratum corneum. Liposomes do not appear to function as permeation enhancers but seem to provide the needed physicochemical environment for transfer of interferon into the skin.
Article
measurement the ear plugs were homogenized in physiological saline containing 0.1% of hexadecyltrimethylammonium bromide. The post 15,000 g supernatants of the homogenates (which contained more than 95% of the PA) were used for the assay [5]. PA units are expressed as nmoles of tetraguaiacol/min at 25~ Results and discussion
Article
A simple assay method for measuring myeloperoxidase (MPO) has been developed. MPO is found in polymorphonuclear leukocytes and is important as a bactericidal agent in the presence of H2O2 and halide ions. This improved assay method is based on work of Andrews and Krinsky using tetramethylbenzidine (TMB) a noncarcinogenic substrate. By assaying MPO under optimal conditions of TMB at 1.6 mM, H2O2 concentration of 0.3 mM, pH 5.4, and incubation temperature of 37 degrees C, sensitivity of MPO measurements increased eightfold in comparison with the original TMB method. A method has been established to determine absorbance at 655 nm of the reaction mixture by incubation for 3 min and then stopping the reaction by the addition of pH 3.0 buffer. An attempt was also made to raise the sensitivity by using 3,3'-dimethyoxybenzidine (DMB), a carcinogenic substrate. The improved TMB method was 34 times more sensitive than the DMB method.
Article
The importance of early microcirculatory changes in the rat colon after exposure to acetic acid was investigated. Administration of 4% acetic acid for 15 sec into an exteriorized colonic segment induced a marked, transient (starting 2 min after the challenge with acetic acid and persisting for 15 min) decrease in the colonic blood flow as estimated by a laser-Doppler flowmeter. Four days after acetic acid administration, a uniform colitis had developed in the exteriorized colonic segment with a total morphological score (TMS) of 15.1 +/- 0.8, myeloperoxidase activity (MPO) increased more than threefold, and plasma exudation into the colonic lumen increased sevenfold. Administration of hydrochloric acid (HCl) with the same pH as the acetic acid or sodium acetate (pH 7.0) did not affect colonic blood flow or produce colitis. Mechanical colonic ischemia, induced by a controlled increase in the intraluminal pressure, resulted in several pathological features of colitis with a TMS of 7.3 +/- 0.2, combined with a significant increase in MPO activity. The TMS and MPO were further increased when mechanical colonic ischemia was combined with HCl or sodium acetate. Pretreatment with SOD and catalase 5 or 15 min before acetic acid administration did not affect the transient ischemia immediately following acetic acid administration. However, it partially prevented the development of colitis. It is concluded that immediate transient ischemia accompanied by the generation of oxygen free radicals might be of importance in the pathogenesis of acetic acid-induced colitis in the rat.
Article
An enzyme immunoassay (EIA) for phycocyanin in foods was developed. Anti-phycocyanin monoclonal antibodies were obtained from A/J mice immunized with phycocyanin. The phycocyanin in a food was extracted by dissolving the sample in a borate buffer solution, pH 8.0 (BBS) and adjusting the pH value of this solution to 8.0 with NaOH. The extract was then diluted more than 10 fold with 1% gelatin in BBS. Phycocyanin was determined by avidin-biotin sandwich EIA, using the P26-8 monoclonal antibody as the solid-phase antibody and the P277-4 monoclonal antibody as the enzyme-labeled antibody. The working range for a quantitative analysis was 100-1000 ng/ml, and the detection limit was 10 micrograms/g of the original sample. Recoveries of phycocyanin from foods by this assay were > 71% for candy, and > 66% for ice cream and sherbet. Phycocyanin was assayed in 22 blue-, green-, purple-, and brown-colored commercial foods, and detected in one green colored-jelly at 49 micrograms/g.
Article
The anti-inflammatory effect of c-phycocyanin extract was studied in acetic acid-induced colitis in rats. Phycocyanin (150, 200 and 300 mg kg-1 p.o.) was administered 30 min before induction of colitis with enema of 1 ml of 4% acetic acid per rat. Twenty-four hours later myeloperoxidase (MPO) activity was determined as well as histopathological and ultrastructural studies were carried out in colonic tissue. Phycocyanin substantially reduced MPO activity which was increased in the control colitis group. Also, histopathological and ultrastructural studies showed inhibition in inflammatory cell infiltration and reduction to some extent in colonic damage in rats treated with phycocyanin. The probable role of antioxidative and the scavenging properties of phycocyanin against reactive oxygen species in the anti-colitic effect is discussed in this paper. To our knowledge this is the first report on the anti-inflammatory effect of phycocyanin in an experimental model of colitis.(c) 1999 The Italian Pharmacological Society.
Article
The anti-inflammatory effect of c-phycocyanin extract was studied in acetic acid-induced colitis in rats. Phycocyanin (150, 200 and 300 mg kg(-1) p.o.) was administered 30 min gbefore induction of colitis with enema of 1 ml of 4% acetic acid per rat. Twenty-four hours later myeloperoxidase (MPO) activity was determined as well as histopathological and ultrastructural studies were carried out in colonic tissue. Phycocyanin substantially reduced MPO activity which was increase din the control colitis group. Also, histopathological and ultrastructural studies were carried out in colonic tissue. Phycocyanin substantially reduced MPO activity which was increased in the control colitis group. Also, histopathological and ultrastructural studies showed inhibition in inflammatory cell infiltration and reduction to some extent in colonic damage in rats treated with phycocyanin. The probable role of antioxidative and the scavenging properties of phycocyanin against reactive oxygen species in the anti-colitic effect is discussed in this paper. To our knowledge this is the first report on the anti-inflammatory effect of phycocyanin in an experimental model of colitis.
Article
To determine whether quantification of myeloperoxidase (MPO) activity could be a useful laboratory technique to detect granulocyte infiltration in equine intestinal tissues. Intestinal tissue (inflamed or healthy) collected from 16 age- and sex-matched Shetland Ponies. Intestinal tissue MPO activity was determined, and histologic assessment of adjacent specimens from healthy and inflamed intestine was done. Intestinal tissue MPO activity and histopathologic score increased with time after castor oil challenge and peaked at 16 hours in an equine diarrhea model in which individual ponies provided their own control tissues. Intestinal tissue inflammation scores correlated positively with tissue MPO activity in adjacent specimens. Tissue MPO assay may be a useful laboratory tool to quantify intestinal mucosal inflammation in ponies.
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The dermal and transdermal delivery of protein pharmaceuticals faces enormous challenges, and at the same time has very significant potential for the non-invasive treatment of both localized and systemic diseases. In this article we review the various approaches used to enhance and control the delivery of protein therapeutic agents through the dermal barrier. We show results of the delivery of interferon (IFN) alpha, an antiviral agent used in the treatment of condylomata acuminata (genital warts), using lipid-based delivery systems (LBDS). In the general category of LBDS, we investigated the use of liposomes and fatty acylation as ways to increase IFNalpha delivery into human skin.
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C-Phycocyanin (from Spirulina platensis) effectively inhibited CCl(4)-induced lipid peroxidation in rat liver in vivo. Both native and reduced phycocyanin significantly inhibited peroxyl radical-induced lipid peroxidation in rat liver microsomes and the inhibition was concentration dependent with an IC(50) of 11.35 and 12.7 microM, respectively. The radical scavenging property of phycocyanin was established by studying its reactivity with peroxyl and hydroxyl radicals and also by competition kinetics of crocin bleaching. These studies have demonstrated that phycocyanin is a potent peroxyl radical scavenger with an IC(50) of 5.0 microM and the rate constant ratios obtained for phycocyanin and uric acid (a known peroxyl radical scavenger) were 1.54 and 3.5, respectively. These studies clearly suggest that the covalently linked chromophore, phycocyanobilin, is involved in the antioxidant and radical scavenging activity of phycocyanin.
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We report data from two related assay systems (isolated enzyme assays and whole blood assays) that C-phycocyanin a biliprotein from Spirulina platensis is a selective inhibitor of cyclooxygenase-2 (COX-2) with a very low IC(50) COX-2/IC(50) COX-1 ratio (0.04). The extent of inhibition depends on the period of preincubation of phycocyanin with COX-2, but without any effect on the period of preincubation with COX-1. The IC(50) value obtained for the inhibition of COX-2 by phycocyanin is much lower (180 nM) as compared to those of celecoxib (255 nM) and rofecoxib (401 nM), the well-known selective COX-2 inhibitors. In the human whole blood assay, phycocyanin very efficiently inhibited COX-2 with an IC(50) value of 80 nM. Reduced phycocyanin and phycocyanobilin, the chromophore of phycocyanin are poor inhibitors of COX-2 without COX-2 selectivity. This suggests that apoprotein in phycocyanin plays a key role in the selective inhibition of COX-2. The present study points out that the hepatoprotective, anti-inflammatory, and anti-arthritic properties of phycocyanin reported in the literature may be due, in part, to its selective COX-2 inhibitory property, although its ability to efficiently scavenge free radicals and effectively inhibit lipid peroxidation may also be involved.
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Salvia officinalis L. leaves, obtained from four plant populations of different origin, were investigated for their topical anti-inflammatory properties. The n-hexane and the chloroform extracts dose-dependently inhibited the Croton oil-induced ear oedema in mice, the chloroform extracts being the most active. By contrast, the methanol extracts showed a very low effect and the essential oil was inactive. Chemical and pharmacological investigation of the most potent chloroform extract, issued from an autochthonous sage population grown in the submediterranean climatic region of Slovenia, revealed ursolic acid as the main component involved in its anti-inflammatory activity. The anti-inflammatory effect of ursolic acid (ID50 = 0.14 microMoles/cm2) was two fold more potent than that of indomethacin (ID50 = 0.26 microMoles/cm2), which was used as a reference non-steroidal anti-inflammatory drug (NSAID). The content of ursolic acid in sage and sage-based remedies for the topical treatment of inflammatory diseases is proposed as a parameter for quality control purposes.