Drug Deposition In Skin Research Articles

Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer.

Photodynamic therapy (PDT) to manage non-melanoma skin cancers has garnered great attention over the past few years. Hypericin (Hy) is a potent lipid-soluble photosensitiser with promising anticancer therapeutic activities. Nevertheless, its poor water-solubility, aggregation in biological systems and insufficient skin penetration restricted its effective exploitation. Herein, we report for the first-time encapsulation of Hy into lipid nanocapsules (Hy-LNCs), and then application of an AdminPen™ hollow microneedles (Ho-MNs) array and an in-house fabricated Ho-MN to enable efficient intradermal delivery. The physicochemical properties, photoactivity, ex vivo drug distribution and cellular uptake were evaluated. Results showed that Hy-LNCs were successfully formed with a particle size of 47.76±0.49nm, PDI of 0.12±0.02, high encapsulation efficiency (99.67%±0.35), 396 fold higher photoactivity, 7 fold higher skin drug deposition, significantly greater cellular uptake and higher photocytotoxicity compared to free Hy. The therapeutic effect of Hy-LNCs was finally assessed in vivo using a nude mouse model with transplanted tumours. Interestingly, Hy-LNCs delivered by Ho-MN exhibited remarkable anti-tumour destruction (85.84%) after irradiation with 595nm. This study showed that Ho-MNs-driven delivery of Hy-LNCs followed by irradiation could form a promising minimally invasive, effective and site-specific approach for managing non-melanoma skin cancers.

Design, optimization and in-vivo characterization of mupirocin loaded nanostructured lipid carrier based gel for effective treatment of impetigo

Mupirocin is a broad-spectrum antibiotic effective in treatment of skin infection (Impetigo), but the poor bioavailability limits its use as a conventional dosage form such as tablets, ointment and cream. The present investigation was aimed to design, optimize and evaluate Mupirocin (MC) loaded nanostructured lipid carriers (NLCs) based gel for topical application. Excipients identified were screened for apposite material required for the formulation of NLCs using process variables as the determining factors. The preparation of nanostructured lipid carriers (NLCs) was optimized using 32 factorial design with two independent variables (solid: liquid lipid ratio and surfactant (%)) and two responses (particle size (nm), entrapment efficiency (%)) using hot high pressure homogenization method. The formulation was further characterized for zeta potential (mV), polydispersity index and morphology. The optimized NLC dispersion of Mupirocin (MC) was lyophilized and loaded in 0.75% w/v Carbopol 980 gel and was evaluated for pH, viscosity and drug content. Mupirocin (MC) loaded NLC based gel were characterized for ex-vivo drug permeation and compared with marketed (cream) preparation. Further, drug deposition, skin irritation and stability study was carried out as per ICH guidelines. The optimized formulation (F5) containing Glyceryl behenate: Oleic acid (70:30), and Poloxamer 188 (0.5%) demonstrated smaller particle size (150.02 ± 1.52 nm) with higher drug entrapment efficiency (88.02 ± 1.21%). Mupirocin (MC) loaded NLC based gel demonstrated sustained drug profile with significant increase (P < 0.05) in drug deposition in skin (about 26%) with non-irritant properties to the skin. Stability study showed no significant changes of the parameters during and after the study. In conclusion, developed Mupirocin (MC) loaded NLC based gel could serve as a novel approach in treatment of impetigo by deliver the drug topically with sustained effect and improved patient compliance.

Cellulose microsponges based gel of naringenin for atopic dermatitis: Design, optimization, in vitro and in vivo investigation

Naringenin, a bioflavonoid, is a natural alternative for atopic dermatitis that possesses anti-inflammatory, antioxidant and photo-protective action. The primary objective of this study is to prepare and evaluate naringenin-loaded microsponge gel for dermatitis. Ethyl cellulose based microsponges of naringenin were prepared by quasi-emulsion-solvent diffusion and statistically optimized by 32 factorial design. After in vitro characterization, optimized microsponge batch (Trial 3) was incorporated into Carbopol base to prepare 1% naringenin-loaded microsponge gel (NGMSG1%) which was evaluated for skin irritation, in vivo efficacy and drug deposition in DNFB-challenged albino Wistar rats in comparison to 1% plain naringenin gel (NGG1%). The average particle size and in vitro drug release of optimized microsponge formulation was observed to be 180 μm and 92.3% ± 2.37 at the end of 24 h, and entrapment was achieved till 82%. SEM study confirmed porous, spherical shaped microsponges whereas FTIR and DSC data supported the formation of microsponges. No skin irritation was observed with NGMSG and NGG in animals. NGMSG1% showed faster healing, substantial reduction in thickness of swollen earflap and WBC count than NGG1%. Similarly, NGMSG showed 3-fold greater drug deposition in skin than plain gel. Thus, naringenin loaded microsponge gel can be further explored as natural remedy for atopic dermatitis.

Development and in-vitro evaluation of co-loaded berberine chloride and evodiamine ethosomes for treatment of melanoma.

Berberine chloride (BBR) and evodiamine (EVO) are two main active ingredients of "ZuoJinWan", a classical Chinese herbal medicine, and these compounds are known to have a synergistic inhibitory effect on various cancer cell lines. Several recent studies have reported anti-melanoma effects for both BBR and EVO. However, topical delivery of the two compounds has been challenging, due to their poor aqueous solubility and their low skin penetration. In the current study, we have combined BBR and EVO into an ethosomes delivery system with the future aim to design a novel topical anti-melanoma formulation. The ethosomes formulations were characterized using particle size, entrapment efficiency and an in vitro skin drug deposition study. The ethosome formulation displaying maximum drug deposition in the epidermis was selected for further study. This formulation contained ethosomes with mean size of 171nm and 90% or above entrapment efficiency for both BBR and EVO. Cell viability tests proved the optimized ethosomes increased the inhibitory effect on B16 melanoma cells. These results corroborate that ethosomes containing a combination of BBR and EVO are a promising delivery system for potential use in melanoma therapy.

Resveratrol-loaded nanoemulsion gel system to ameliorate UV-induced oxidative skin damage: from in vitro to in vivo investigation of antioxidant activity enhancement.

In the present study resveratrol nanoemulsion gel was developed and optimized with the aim of enhancing the permeability and antioxidant activity against ultraviolet (UV)-induced oxidative skin damage. Droplet size, polydispersity index, drug permeation flux, permeability coefficient and drug deposition in skin of resveratrol-loaded nanoemulsion were found to be 65.00 ± 5.00nm, 0.171 ± 0.082, 144.50μg/cm2/h, 2.90 × 10-2cm/h and 45.65 ± 4.76%, respectively, whereas drug permeation flux, permeability coefficient and drug deposition in skin from nanoemulsion gel were found to be 107.70μg/cm2/h, 2.06 × 10-2cm/h and 62.65 ± 4.98%, respectively. Confocal studies depicted deeper penetration of resveratrol from nanoemulsion gel. Differential scanning calorimetry and Fourier-transform infrared spectrophotometer studies confirmed that nanoemulsion gel enhanced fluidization of stratum corneum lipids and conformational disruption of lipid bilayer, thereby enhancing skin permeation of resveratrol. Histopathology study of skin revealed that resveratrol-loaded nanoemulsion gel inhibited UV-induced spongosis, edema and epidermal hyperplasia response. Levels of glutathione, superoxide dismutase, catalase and protein carbonyl in the skin of UV-irradiated rats were significantly (p < 0.01) improved in the skin of animals treated with nanoemulsion gel. Experimental results suggested that nanoemulsion gel could be explored as a promising carrier for topical delivery of resveratrol for prevention of UV-induced oxidative skin damage owing to its enhanced permeability and retention effect.

Synthesis and evaluation of topical hydrogel membranes; a novel approach to treat skin disorders.

The aim of the study was to synthesize and evaluate chitosan-based topical cross-linked hydrogel membranes of mupirocin for new pharmaceutical controlled release application. These cross-linked structured membranes were synthesized by modification of free radical polymerization. Low molecular weight (LMW) chitosan is cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with a crosslinker N,N-methylenebisacrylamide (MBA). Hydrogel membranes were characterized by FTIR, DSC, TGA, SEM, Swelling behavior, sol-gel analysis, in vitro percent drug release at different pH, permeation across skin, ex vivo drug deposition study, irritation study and in vivo antibacterial activity of mupirocin loaded hydrogels. Developed membranes were spherical, adhesive and have good elastic strength. FTIR confirmed the cross-linking and formation of new structure having appropriate characteristics needed for controlled release delivery system. Drug release through rabbit's skin was evaluated by Franz diffusion cell and up to 6329.61 µg/1.5 cm2 was permeated and drug deposition in skin revealed significant retention up to 1224 µg/1.5 cm2. Formulated membranes were nonirritant to the skin as validated by Draize patch test. In surgical wound model, LMW chitosan-based hydrogel membranes showed prolong efficacy against bacterial infection caused by S. aureus. Enhanced retention of drug in skin demonstrated the good potential of topical delivery for skin bacterial infection.

Carbomer gel bearing methotrexate loaded lipid nanocontainers shows improved topical delivery intended for effective management of psoriasis

The present investigation reports the evaluation of potential use of Carbomer gel bearing methotrexate loaded nanostructured lipid carriers for topical application of methotrexate for possible therapy of psoriasis in comparison to solid lipid nanoparticles. These were evaluated for various parameters such as particle size, surface charge, entrapment efficiency, shape and surface morphology, thermal analysis, in-vitro drug release through skin (Franz diffusion cell) and drug deposition study, fluorescence microscopy, particle-skin interaction study, skin-irritation testing and storage stability. The formulation (NLC5) showed the best entrapment efficiency (62.72 ± 0.94%) while SLN showed only 26.84 ± 0.64% with particle size of 221 ± 14nm and 212 ± 11nm, respectively. Skin permeation study of MTX loaded SLN and NLC5 hydrogels showed prolonged drug release up to 24 h. The skin drug deposition study showed the greatest deposition of drug enriched NLC5 hydrogel (28.8%) when compared to plain drug enriched hydrogel (11.4%) and drug enriched SLN hydrogel (18.6%). Fluorescence microscopy suggested the localization effect of these lipid based systems to deeper skin region. The primary skin irritation studies indicated that MTX loaded SLN or NLC5 hydrogels resulted no erythema. It can be concluded that NLC represents a promising particulate carrier having prolonged drug release, improved skin permeation.

5-Fluorouracil ethosomes – skin deposition and melanoma permeation synergism with microwave

This study focuses on the use of ethosome and microwave technologies to facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion technique and had their size, zeta potential, morphology, drug content and encapsulation efficiency characterized. The skin was pre-treated with microwave at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in vitro and in vivo skin drug permeation as well as retention evaluation. The drug and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28 melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted significant drug deposition in skin from ethosomes in vitro while keeping the level of drug permeation unaffected. Similar observations were obtained in vivo with reduced drug permeation into blood. Combination ethosome and microwave technologies enhanced intracellular localization of ethosomes through fluidization of cell membrane lipidic components as well as facilitating endocytosis by means of clathrin, macropinocytosis and in particularly lipid rafts pathways. The synergistic use of microwave and ethosomes opens a new horizon for skin malignant melanoma treatment.

A novel elastic liposome for skin delivery of papain and its application on hypertrophic scar

This study aims to investigate the therapeutic effects of papain elastic liposomes (PEL) on hypertrophic scar through topical application. PEL were prepared using the reverse-phase evaporation method and optimized by response surface methodology. The transdermal absorption of optimized PEL was tested by vertical Franz diffusion cells in vitro. The effects of PEL were investigated in rabbit model of hypertrophic scar in vivo, histological analysis and scar-related proteins were detected to reveal potential scar repair mechanism. The best formulation of PEL had EE (43.8±1.4%), particle size (100.9±2.2nm), PDI (0.037±0.003), zeta potential (-26.3±1.3mV), and DI (21.9±3.1). PEL gave the cumulative amounts and steady state fluxes in the receiver solution of 381.9±32.4μg/cm2, 11.4±1.5μg/cm2/h, and showed drug deposition in skin of 19.1±3.2% after 24h. After topical application, the scar elevation index, microvascular density, and collagen fiber were significantly decreased with regular arrangement. The expressions of TGF-β1, P-Smad-3, P-NF-κB p65, and P-IKBa in hypertrophic scar were significantly down regulated in contrast with those in model group. PEL were proven as an excellent topical preparation for hypertrophic scar treatment.

Enhanced antioxidation via encapsulation of isooctyl p-methoxycinnamate with sodium deoxycholate-mediated liposome endocytosis

Isooctyl p-methoxycinnamate(OMC) is a commonly used chemical ultraviolet B sunscreen that suffers rapid degradation with current delivery systems following sun exposure. In this study, deoxycholate-mediated liposome (DOC-LS) endocytosis was employed to improve the antioxidation effects of OMC following topical administration, and the in vitro cell uptake was investigated to understand the enhanced cutaneous absorption of the drug via this nanocarrier. Following topical application, structural changes in the stratum corneum were identified. With the increase of DOC content, the drug deposition in skin decreased; from this, a DOC-LS formulation was selected that showed significantly more drug delivery in skin than did the other preparations (P<0.05). DOC-LS decreased skin resistance, suggesting its ability to induce skin barrier disruption. In vitro HaCaT keratinocyte cell uptake of coumarin-6 incorporated in the two types of phosphatidylcholine (PC) vesicles (i.e., LS or DOC-LS) yielded similar fluorescence intensities following incubation for different periods (P<0.05). However, CCC-ESF-1 embryonic fibroblast cell uptake of the fluorescence revealed time-dependence, and the emitted light from DOC-LS incubated cells was stronger than that from cells incubated with LS (P<0.05). These findings might be associated with the endocytic pathway of HaCaT, which mainly exhibited adsorption or physical adhesion of the fluorescent vesicles, whereas CCC-ESF-1 markedly internalized the PC vesicles via the lysosomes, as shown by intracellular fluorescence co-location studies. Following loading with the same amount of OMC, the DOC-LS vesicles exhibited superior skin tissue antioxidative capacity among the preparations tested, corroborating the in vivo skin drug deposition results. Thus, our results suggest that DOC-LS is a promising system for OMC dermal delivery without promoting skin irritation, which is quite advantageous for therapeutic purposes.

Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia

Context: Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia.Objective: The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia.Methods: Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively.Results: The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug.Conclusion: It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.

Transcutaneous delivery of leflunomide nanoemulgel: Mechanistic investigation into physicomechanical characteristics, in vitro anti-psoriatic and anti-melanoma activity

The present study is a mechanistic validation of ‘proof of concept’ of effective topical delivery of leflunomide (LFD) nanoemulgel for localized efficient treatment of psoriatic lesions as well as melanoma affected skin regions. Hyperproliferation of keratinocytes in psoriasis and symbiotic relationship between keratinocytes and melanocytes, justifies the need of dual acting treatment. LFD is recently introduced significantly effective disease modifying anti-rheumatic drug and has been considered valuable for the treatment of psoriatic arthritis as well as melanoma. Current available treatments for psoriasis and melanoma are inefficient due to systemic side effects, poor transcutaneous permeation and thus present a challenge for development of novel colloidal carriers. We newly reformulated LFD as a nanoemulgel based on self nanoemulsifying technique using Capryol 90, Cremophor EL, Transcutol HP as nanoemulsifying components and Pluronic F127 as a gelling agent. This thermodynamically stable nanoemuslsifying preconcentrate after gelation showed mean globule size, 123.7nm and viscosity 9620±93cp. Complete mechanical characterization was carried out using Texture Analyzer and hardness, adhesiveness and springiness index were found to be 523gms, 431gms and 1.02, respectively. Ex vivo permeation through rat abdominal skin revealed significant improvement in flux, apparent permeability coefficient, steady state diffusion coefficient and drug deposition in skin due to nanoemulsification of LFD. The in vitro cytoxicity of LFD nanoemulgel in human HaCaT, melanoma A375 and SK-MEL-2 cell lines showed significantly enhanced therapeutic response. In gist, LFD nanoemulgel for trancutaneous delivery will reduce the overall dose and drug consumption, by effectively localizing at the applied target site and will ultimately minimize systemic side effects.

Solid Lipid Nanoparticles Formulated for Transdermal Aconitine Administration and Evaluated In Vitro and In Vivo.

In this study, solid lipid nanoparticles were formulated for transdermal delivery of aconitine to improve its safety and permeability. Aconitine-loaded solid lipid nanoparticles were formulated as an oil-in-water microemulsion. Drug encapsulation efficiencies for these formulations were higher than 85%, and correlated positively with levels of surfactant and oil matrix. The size of the solid lipid nanoparticles was increased with an increase of the oil matrix, and reduction of the surfactant levels. Compared with an ethanol tincture, all the tested solid lipid nanoparticle formulations achieved improved transdermal fluxes and drug deposition in skin in vitro. Real-time monitoring of drug distribution in rat dermis using in vivo microdialysis showed that aconitine concentration was markedly higher following application of solid lipid nanoparticles, compared to tincture, throughout the experimental period. A regional comparison of rat skin found that application of solid lipid nanoparticles to the scapular region resulted in higher AUC(0-t) and C(max), compared to those achieved with application to the abdomen or chest (p < 0.05). In contrast, the application to the chest resulted in the lowest AUC(0-t) and C(max). Together with findings of a structural study of the skin, these results indicated that the drug accumulated more readily in thicker skin regions, and to a lesser extent in well-perfused skin, because of drug transfer to capillaries. The superior transdermal permeability of aconitine-loaded solid lipid nanoparticles contributed to stronger anti-inflammatory and analgesic effects on mouse in vivo models of pain than the tincture (p < 0.05). In vitro and in vivo studies indicated that smaller particle sizes of solid lipid nanoparticles enhanced the transdermal permeability of aconitine, which can promote drug efficacy, reduce administration time, and improve medication safety.

Topical delivery of Idebenone using nanostructured lipid carriers: evaluations of sun-protection and anti-oxidant effects

The objective of present study was to develop nanostructured lipid carriers (NLC) for topical delivery of antioxidant drug and evaluation of its sun protection efficacy. In the present study attempts have been made to formulate Idebenone loaded nanostructured lipid carriers (INLC) by using solvent precipitation method. Preformulation study evidenced for selection of Captex 500 P as an oil phase in which Idebenone has saturation solubility of 0.266 ± 0.032 g/ml. Compritol 888 ATO and ethanol were selected as solid lipid and solvent respectively. Surfactant and co-surfactant as Labrasol and Transcutol P have given stable formulations on the basis of HLB required for stabilization, respect to oil phase. INLC has particle size of 605 ± 4.01 nm and %EE of 82.58 ± 2.20 %. Optimized batches were subjected for crystallographic investigation, in vitro skin permeation study, drug deposition study, SPF determination and antioxidant activity. XRD, DSC studies illustrated that partial amorphization of Idebenone by molecularly dispersion within lipid blend leads for entrapment of drug. Permeation data showed that optimized INLC has flux value (Jss) of 7.87 μg cm−2 h−1. High significance (P < 0.001) of drug deposition in skin was observed between INLC and plain Idebenone gel. SPF value for INLC has 23 which represents that lipid nanocarriers have standards of blocking of 94–96 % of UVB rays. Such high skin deposition and SPF leads to more antioxidant effect of formulations. Hence lipid nanocarriers such as NLC have potential as an antioxidant and sun protection for topical drug delivery.

Ligustrazine Phosphate Ethosomes for Treatment of Alzheimer’s Disease, In Vitro and in Animal Model Studies

In the present study, we have investigated transdermal administration of ligustrazine phosphate (LP), as an antioxidant, for the treatment of Alzheimer's disease (AD). The LP transdermal ethosomal system was designed and characterized. Franz-type diffusion cells and confocal laser scanning microscopy were used for the in vitro permeation studies. Furthermore, the effect of LP transdermal ethosomal system on AD was evaluated in the scopolamine-induced amnesia rats by evaluating the behavioral performance in the Morris water maze test. The activities of the antioxidant enzymes and the levels of the lipid peroxidation product malondialdehyde (MDA) in the brain of rats were also determined. The results showed that both the penetration ability and the drug deposition in skin of the LP ethosomal system were significantly higher than the aqueous one. The LP transdermal ethosomal system could recover the activities of the antioxidant enzymes and the levels of MDA in the brain of the amnesic rats to the similar status of the normal rats, which was also indirectly reflected by the improvement in the behavioral performance. In conclusion, LP might offer a potential alternative therapeutic drug in the fight against AD, and ethosomes could be vesicles of choice for transdermal delivery of LP.

Formulation and optimization of nano-sized ethosomes for enhanced transdermal delivery of cromolyn sodium

Aim:The current study was aimed to investigate the feasibility of transdermal delivery of cromolyn sodium using a novel lipid vesicular carrier, ethosomes.Materials And Methods:Ethosomes of cromolyn sodium was prepared, optimized, and characterized for vesicle shape, vesicle size and size distribution, zeta potential, entrapment efficiency, in vitro drug release, in vitro skin permeation, in vitro skin deposition and vesicle stability. Histological examination of porcine ear skin treated with optimized ethosomal formulation was performed to study the change of skin morphologies.Results:The optimized cromolyn sodium ethosomes showed reasonable entrapment efficiency (49.88±1.84%), optimum nanometric size range (133.8 ± 7.5 nm), and high zeta potential (-69.82 ± 1.2 mV). In vitro drug release studies of optimized ethosomal formulation through cellophane membrane showed an enhanced and sustained delivery of drug compared to conventional liposomes, hydroethanolic, (45% v/v) and phosphate buffer saline PBS pH 7.4 drug solutions. The optimized ethosomal formulation showed significantly-enhanced transdermal flux (18.49 ± 0.08 mg/cm2/h) across porcine ear skin as compared to liposome (1.80 ± 0.12 mg/cm2/h), hydroethanolic drug solution (4.45 ± 0.71 mg/cm2/h), and PBS pH 7.4 drug solution (1.18 ± 0.35 mg/cm2/h). Moreover, ethosomal formulation showed better skin drug deposition (10.28 ± 0.67%) and shortest lag time (0.11 ± 0.09 h) for cromolyn sodium.Conclusion:Our significant results suggest that ethosomes can be a promising tool for transdermal delivery of cromolyn sodium.

Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis

Introduction:Betamethasone dipropionate (BD) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the current work was to test the hypothesis that the addition of corticosteroid such as BD and a keratolytic agent such as salicylic acid in nanocarrier based microemulsions formulation would result in enhancement and sustaining of corticosteroid delivery rate leading to better anti-psoriatic activity. Clinical use of BD is restricted to some extent due to its poor permeability across the skin. So to increase its permeation across the skin, microemulsion-based gel formulations were prepared and characterised.Materials and Methods:Microemulsions were prepared by aqueous phase titration method, using oleic acid:sefsol (1.5:1), Tween 20, isopropyl alcohol, and distilled water as the oil phase, surfactant, cosurfactant and aqueous phase, respectively. Selected formulations were subjected to physical stability studies and consequently in vitro skin permeation studies. Surface studies of optimized formulation were done by transmission electron microscopy. In vivo anti-inflammatory activity was done by carageenan-induced raw paw edema method.Results:The droplet size of microemulsions ranged from 60 to 190 nm. The optimized formulation exhibited viscosity 28.55 ± 2.03 mP, refractive index 1.409, pH 6.4, and conductivity 10-4 scm-1. The optimized microemulsion was converted into hydrogel using carbopol 934, and salicylic acid was incorporated into it. Drug deposition in skin was found to be 29.73 μg/mg. Assessment of skin permeation was done by histopathology studies which indicated changes in the structure of epidermal membrane of skin. In vivo anti-inflammatory activity indicated 72.11% and 43.96% inhibition of inflammation in case of developed microemulsion gel and marketed gel, respectively.Conclusions:The developed microemulsion gel containing BD and salicylic acid provided sustained and good anti-inflammatory activity for the treatment of psoriasis.

Skin Delivery of Ferulic Acid from Different Vesicular Systems

The aim of the present research is to evaluate the skin delivery capabilities of different vesicular systems, including conventional liposomes (CL), Tween 80-based deformable liposomes (DL), invasomes (INS) and ethosomes bearing ferulic acid (FA) being an antioxidant exhibiting a wide range of therapeutic effects against various diseases. All of the test formulations were characterized for particle size distribution, zeta-potential, vesicular shape and surface morphology, in vitro human skin permeation and skin deposition. Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) defined that all of liposomal vesicles were almost spherical, displaying unilamellar structures with low polydispersity (PDI < 0.2) and nanometric size range (z-average no more than 150 nm). In addition, all the vesicular systems except conventional liposomes were negatively charged to a certain extent. In vitro skin permeation and skin deposition experiments demonstrated that the permeation profile of ferulic acid through human stratum corneum epidermis membrane (SCE) and the drug deposition in skin were both improved significantly using these vesicular liposomal systems. Permeation and skin deposition enhancing effect was highlighted by the ethosomal system containing 18.0 mg/ml of ferulic acid with an significantly (P < 0.01) enhanced skin flux (267.8 +/- 16.77 microg/cm2/h) and skin drug deposition (51.67 +/- 1.94 microg/cm2), which was 75 times and 7.3 times higher than those of ferulic acid from saturated PBS (pH 7.4) solution, respectively. This study demonstrated that ethosomes are promising vesicular carriers for delivering ferulic acid into or across the skin.

Elastic Liposomes Mediated Transdermal Delivery of An Anti-Jet Lag Agent:Preparation, Characterization and In Vitro Human Skin Transport Study

In order to get across the intact skin, drug-laden carriers have to pass through narrow, confining pores of 50 nm or less diameter, under the influence of a suitable transdermal gradient. Novel ultradeformable carriers, the elastic liposomes achieve this target via its deforming and self-optimizing property. The main goal of this work was to prepare and characterize, elastic liposomes bearing melatonin, an anti-jet lag agent for its efficient transdermal delivery. Elastic liposomes bearing melatonin were prepared by modified extrusion method and characterized for shape, lamellarity, size distribution, percent drug loading, turbidity profile by Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Mini-column centrifugation and Nephelometric techniques. The effect of different formulation variables like type of surfactant and concentration of surfactant on the deformability of vesicles, turbidity changes, transdermal flux across human cadaver skin, amount of drug deposited into the skin were investigated. Confocal laser scanning (CLS) micrographs revealed that probe (Rhodamine Red) loaded elastic liposomes were able to penetrate much deeper than the probe loaded conventional rigid liposomes. Out of the three surfactants utilized namely, Span 80, Sodium cholate and Sodium dodecylsulphate, formulation bearing Span 80 at an optimum lipid: surfactant ratio of 85:15% w/w proved to be the best in all parameters studied. The optimum skin permeation profile including greater transdermal flux and lower lag time of melatonin from optimized elastic liposomes via human cadaver skin was observed. Our results of the present study demonstrated the feasibility of elastic liposomal system for transdermal delivery of this anti- jet lag agent, which provides better transdermal flux, higher entrapment efficiency, greater skin drug deposition and possesses the ability of a self-penetration enhancer as compared to conventional liposomes.