Skin Deposition Studies Research Articles

Topical Delivery of Fenugreek Seed Extract Loaded Solid Lipid Nanoparticles Based Hydrogels for Alopecia

Background: Alopecia, a chronic dermatological inflammatory condition affecting the hair follicles. Conventional treatments are associated with the risk of serious side effects. The stratum corneum limits the percutaneous absorption of drugs. Hence, the development of novel herbal formulations for topical delivery has been the target, with the enhancement of their therapeutic efficacy and safety of use.
 Aims: To formulate and characterize Fenugreek seed extract loaded solid lipid nanoparticles carrier for the management of Alopecia to reduce the systemic side effects.
 Methodology: Fenugreek seed extract loaded solid lipid nanoparticles (SLN) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Tween 80, and Soya lecithin as Lipid, Surfactant, and Co-Surfactant. The SLN was incorporated into carbapol 934 dispersion to convert it into a gel. The SLN formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency, Transmission Electron Microscopy. After that, the SLN gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, and Skin deposition studies.
 Results: The formulated Fenugreek seed extract loaded showed a particle size of 223.36 nm with a narrow PDI of 0.313. Entrapment efficiency revealed that 74.56±0.12% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the SLN. The extended-release pattern of the formulated SLN for 24h was observed in the in vitro release studies and followed Higuchi model(R2=0.9964). Ex vivo permeability showed a 72.05±0.15% deposition of Fenugreek seed extract loaded SLN. The formulation was stable for three months without significant changes.
 Conclusion: Fenugreek seed extract loaded NLC demonstrated enhanced permeation, improved skin retention, and extended release compared to conventional gel. The developed formulation would be further used for in vivo studies and by seeing above results it can be an alternative for Alopecia in the future.

DEVELOPMENT AND OPTIMIZATION OF MANNOSYLATED NARINGENIN LOADED TRANSFERSOMES USING RESPONSE SURFACE METHODOLOGY FOR SKIN CARCINOMA

Objective: The flavonoidal drug Naringenin offers a natural defense against free radical generation due to their antioxidant i.e. free radical scavenging property. The continuation of research work towards the invention of targeting the flavonoidal drug for skin carcinoma. Naringenin is a potent antioxidant, having remarkable reactive oxygen species scavenging potential and abundantly found in citrus fruits.
 Methods: The optimization of the formulated mannosylated naringenin-loaded transfersomes (MA-NgTfs) was performed using Box–Behnken statistical design to obtain crucial variable parameters that influence vesicular size, size distribution and surface charge. Therefore keeping both the concepts in mind our objective is to design and optimize the mannosylated naringenin loaded transfersomes (MA-NgTfs) for macropahge targeting. The Box Behnken with 3D surface response design graph was employed to optimize the formulation.
 Results: Phospholipids and surfactant ratio played a remarkable role to determine the mean vesicular size and the Zeta potential of the vesicles. The Zeta potential is found in the formulation having a range of-18.01±1.05 to-28.7±1.008 mV represents the good stability of the formulation. The vesicles size range was found in the range of 102.4±1.01 to 263.74±0.63 and range of Entrapment efficiency of nanovesicles was as 72.04±1.53 to 82.04±0.81. In vitro drug release study shows that mannosylated naringenin loaded transfersomes (MA-NgTfs), and marketed formulation dispersion was found 69.31 %, 62.03 %, 58.71 %, and 65.02 % respectively. Ex vivo skin permeation and deposition study shows that the marketed product and pure drug suspension optimized transfersomes through the skin of mice was of flux 6.5±3.07 and the percentage of drug retention was 0.76±1.26. The results gave us strong evidence of cellular uptake bymannose–directed transfersomes via mannose receptor-based endocytosis.
 Conclusion: On the basis of findings, the study revealed that the prepared formulation has characteristic potential for targeting and the concept of ligand directed nanocarrier formulation was imparts synergistic effect against UV-induced skin carcinoma.

Rapid and simultaneous determination of dexamethasone and dexamethasone sodium phosphate using HPLC-UV: Application in microneedle-assisted skin permeation and deposition studies

Dexamethasone is a fluorinated derivative of the natural glucocorticoid, cortisone, with a very high systemic anti-inflammatory effect. In this study, a simple and rapid high performance liquid chromatography (HPLC) method was developed and validated to quantify dexamethasone and its prodrug dexamethasone sodium phosphate in skin permeation studies. The separation of both the compounds was achieved on a Vydac Denali C18 column(250 × 4.6 mm, 5 μm) with a mobile phase composed of 5 mM ammonium acetate buffer-acetonitrile-methanol (43:32:25, v/v) at a flow rate of 0.9 mL/min and UV detection at 240 nm. The standard curves were found to be linear in the range from 0.5 to 100 µg/mL for both the drugs and the method could successfully separate the drug peaks from interfering peaks of endogenous skin constituents. Accuracy values of both the drugs were within 98.60 to 108.60% (intra-day) and 98.70 to 107.20% (inter-day) and precision values were within 2% at the studied concentrations. The developed method was used to investigate the effect of microneedles on transdermal delivery of dexamethasone sodium phosphate. The hydrolysis of dexamethasone sodium phosphate to dexamethasone in the presence of rat skin homogenate and rat plasma was also evaluated to confirm the conversion that occurs during skin permeation and in the blood circulation. The skin permeation and deposition characteristics of microneedle-assisted diffusion were compared to those achieved by passive diffusion. The observed data demonstrated that transdermal permeation of dexamethasone is significantly enhanced with microneedle pretreatment of rat skin, showing a marked increase in flux and permeability coefficient, compared to passive diffusion. This simple isocratic HPLC method can, be effectively applied for the evaluation of skin permeation of topical/transdermal dexamethasone formulations.

Fabrication of Highly Deformable Bilosomes for Enhancing the Topical Delivery of Terconazole: In Vitro Characterization, Microbiological Evaluation, and In Vivo Skin Deposition Study.

The current study aimed to load terconazole (TCZ), an antifungal agent with low permeability characteristics, into highly deformable bilosomes (HBs) for augmenting its topical delivery. HBs contain edge activator in addition to the constituents of traditional bilosomes (Span 60, cholesterol, and bile salts). More elasticity is provided to the membrane of vesicles by the existence of edge activator and is expected to increase the topical permeation of TCZ. HBs were formulated using ethanol injection technique based on 24 complete factorial design to inspect the impact of various formulation variables (bile salt type and amount, edge activator type, and sonication time) on HBs characteristics (entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP)). The optimum formula (HB14) was decided based on Design-Expert® software and was utilized for further explorations. HB14 exhibited EE% = 84.25 ± 0.49%, PS = 400.10 ± 1.69nm, PDI = 0.23 ± 0.01, and ZP = - 56.20 ± 0.00mV. HB14 showed spherical vesicles with higher deformability index (9.94 ± 1.91g) compared to traditional bilosomal formula (3.49 ± 0.49g). Furthermore, HB14 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition studies revealed superior TCZ deposition inside the skin from HB14 compared to traditional bilosomal formula and TCZ suspension. Moreover, histopathological examination in rats assured the safety of HB14 for topical use. Concisely, the obtained outcomes confirmed the pronounced efficacy of HBs for topical delivery of TCZ.

Co-polymer mixed micelles enhanced transdermal transport of Lornoxicam: in vitro characterization, and in vivo assessment of anti-inflammatory effect and antinociceptive activity

The objective of this study was to develop mixed micelles of Lornoxicam, using a Pluronic® mixture of L121 and P123. The technique used for the preparation was thin-film hydration according to a Box Behnken design with three central points for each formula. The independent variables studied were Pluronic®: drug ratio, Pluronic® L121: Pluronic® P123 ratio and amount of soya-bean lecithin. The studied dependent variables were: percent entrapment efficiency (% EE), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and in vitro LX released (after 2, 10 h). Numerical optimization was used to statistically optimize the formulae using Design-Expert® software. Choosing the best formula was in terms of maximizing % EE, ZP (as absolute value) and in vitro release, while minimizing PS and PDI. Characterization of best formula was performed by Transmission electron microscopy, Differential scanning calorimetry, Fourier transform infrared spectroscopy, stability testing, ex vivo permeation and skin deposition studies using rat skin. The in vivo pharmacodynamics activities of the optimized formula were examined on male rats and mice and related to that of the oral commercial product. The optimized formula demonstrated to be non-irritant, with considerably improved anti-inflammatory and analgesic activities. Higher in vivo skin permeation was confirmed using confocal laser scanning microscopy. In conclusion, the obtained results proved that mixed micelles could be promising method for transdermal drug delivery.

Ethosomal Gel Formulation of Alpha Phellandrene for the Transdermal Delivery in Gout.

Purpose: Purpose was to improve the skin compatibility and permeability of alpha phellandrene through an ethosomal gel formulation for the treatment of gout; as the oral use of the drug is reported to cause gastrointestinal disturbances and toxicities. Methods: Alpha phellandrene loaded ethosomal formulation (APES) was prepared by cold method for the treatment of gout. APES were loaded into carbopol gel (APEG) by dispersion method. Physico-chemical characterizations of the APES were done by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR) etc. In vitro release, permeation, haemo-compatibility and anti-inflammatory studies were conducted. Results: APES showed a particle size of 364.83 ± 45.84 nm. The entrapment efficiency of the optimized formulation is found as 95.06 ± 2.51%. Hemolysis data indicated that APES does not cause any significant hemolysis. In vitro drug release studies were carried out using dialysis membrane technique and the amount of drug released from APES & APEG is found to be 95% and 94.21% respectively after 5 and6 hours. Kinetic data analysis revealed that APES & APEG follows first order and zero order release kinetics, respectively. The anti-inflammatory activity studies of the formulation are done by estimating its inhibitory effects on cyclooxygenase II (COX) II, lipoxygenase-5 (LOX-5), Myeloperoxidase (MPO), Inducible nitric oxide synthase (INOS) & cellular nitrite level using RAW 264.7 cells. The significant inhibition in the activities of the enzymes implies the anti-inflammatory activity of the formulations. Skin permeation study was carried out using porcine skin and revealed that the permeation of alpha phellandrene is increased from APES & APEG when compared with alpha-phellandrene solution (APS). Skin deposition study of APS, APES & APEG revealed better drug deposition from APEG (48.799 ± 1.547µg/cm2 ) after 24 hours when compared with APS & APES. Conclusion: Overall results indicate that the ethosomal formulation of alpha phellandrene through transdermal route is an effective alternative for oral use of the drug.

Development, characterization and evaluation of nanocarrier based formulations of antipsoriatic drug “acitretin” for skin targeting

Acitretin, a 2nd generation retinoid, is a drug of choice for the treatment of severe psoriasis. Presently, only capsule formulation for oral administration is commercially available and associated with limitations of severe systemic side effects. In the present study, carrier elastic liposomal and ethosomal based topical gel formulations were developed, optimized, and characterized in-vitro, ex-vivo, and in-vivo to provide effective skin targeting of acitretin. In-vitro characterization exhibited nanometric vesicle size range (591 ± 16 and 360 ± 14 nm), high encapsulation efficacy (94.7 ± 2.1% and 91.2 ± 1.6%), optimum viscosity (1152 and 1320 cP), thixotropic behavior and good storage stability of the developed formulation. Ex-vivo skin permeation and deposition studies carried on four different biological membranes (rat, mice, porcine ear, and human cadaver skin) showed higher skin deposition of prepared carrier-based gels in comparison to plain acitretin gel. Better skin localization potential was also confirmed by mechanistic studies using Confocal Laser Scanning Microscopy and Scanning Electron Microscopy analysis. In-vivo antipsoriatic activity demonstrated the better therapeutic efficacy of carrier-based formulations. Thus, developed formulation seems to be a safe and promising alternative to oral route for effective topical delivery of acitretin with improved pharmacological activity and no systemic toxicity.

Methotrexate-Loaded Nanostructured Lipid Carrier Gel Alleviates Imiquimod-Induced Psoriasis by Moderating Inflammation: Formulation, Optimization, Characterization, In-Vitro and In-Vivo Studies.

IntroductionMethotrexate exhibits poor cutaneous bioavailability and systemic side effects on topical administration, so there is an unmet need for a novel carrier and its optimized therapy. Methotrexate-loaded nanostructured lipid carriers (MTXNLCs) were formulated and characterized to determine in vitro drug release and evaluate the role of MTXNLC gel in the topical treatment of psoriasis.MethodsA solvent diffusion technique was employed to prepare MTXNLCs, which was optimized using 32 full factorial designs. The mean diameter and surface morphology of MTXNLCs was evaluated. The crystallinity of lyophilized MTXNLCs was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). MTXNLCs were integrated in 1% w/w Carbopol 934 P gel base, and in vitro skin deposition studies in human cadaver skin (HCS) were carried out.ResultsThe optimized MTXNLCs were rod-shaped, with an average particle size of 253 ± 8.65 nm, a zeta potential of −26.4±0.86 mV, and EE of 54.00±1.49%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of MTX was found in HCS from MTXNLC gel (71.52 ±1.13%) as compared to MTX plain gel (38.48±0.96%). In vivo studies demonstrated significant improvement in therapeutic response and reduction in local side effects with MTXNLCs-loaded gel in the topical treatment of psoriasis. Anti-psoriatic efficacy of MTXNLCs 100 ug/cm2 compared with plain MTX gel was evaluated using imiquimod (IMQ)-induced psoriasis in BALB/c mice. The topical application of MTXNLCs to the mouse ear resulted in a significant reduction of psoriatic area and severity index, oxidative stress, inflammatory cytokines like TNF-α, IL-1β, and IL-6 and IMQ-induced histopathological alterations in mouse ear samples.ConclusionDeveloped formulation of MTXNLC gel demonstrated better anti-psoriatic activity and also displayed prolonged and sustained release effect, which shows that it can be a promising alternative to existing MTX formulation for the treatment of psoriasis.

Formulation, optimization, and in vitro evaluation of nanostructured lipid carriers for topical delivery of Apremilast.

This work was aimed to formulate topical Apremilast (APM)-loaded nanostructured lipid carriers (NLCs) for the management of psoriasis. NLCs were prepared by a cold homogenization technique using Compritol 888ATO, oleic acid, Tween 80 and Span 20, and Transcutol P as a solid lipid, liquid lipid, surfactant mixture, and penetration enhancer, respectively. Carbopol 940 was used to convert NLC dispersion into NLC-based hydrogel to improve its viscosity for topical administration. The optimized formulation was characterized for size, polydispersity index (PDI), zeta potential (ZP), percentage of entrapment efficiency (%EE), and surface morphology. Furthermore, viscosity, spreadability, stability, in vitro drug diffusion, ex vivo skin permeation, and skin deposition studies were carried out. APM-loaded NLCs showed a narrow PDI (0.339) with a particle size of 758 nm, a %EE of 85.5%, and a ZP of -33.3 mV. Scanning electron microscopy confirmed spherical shape of NLCs. in vitro drug diffusion and ex vivo skin permeation results showed low drug diffusion, sustained drug release, and 60.1% skin deposition. The present study confirms the potential of the nanostructured lipid form of poorly water-soluble drugs for topical application and increased drug deposition in the skin.

Luliconazole vesicular based gel formulations for its enhanced topical delivery

Luliconazole is a new drug candidate for treatment of topical fungal infections. Its present therapy is associated with limitations of very poor and slow skin permeation, leading to required long term repeated administration for complete cure of disease. Lipid nanocarriers based elastic lipogel and ethogel formulations were developed in strength of 1% w/w and extensively characterized in vitro, ex-vivo, and in vivo and compared for their results to the marketed formulation. The prepared formulations were found to have ideal pH, nanometric vesicle size, encapsulation efficiency (92.7% and 91.2%), zeta potential (−17.0 and −32.8 mV), and viscosity (6.6 and 7.8 Pa.s) with no signs of instability on storage. In vitro activity against Candida albicans and dermatophytes demonstrated the prepared formulations to be 3 and 2.5 times more potent than marketed formulation, respectively. Ex vivo skin permeation and deposition studies, performed on various biological membranes and a synthetic membrane, manifest that Strat-M membrane resembles closest to the human skin followed by porcine ear skin, rat, and mice skin. Enhanced skin deposition of elastic lipogel and ethogel as compared to conventional marketed cream is also confirmed by SEM and CLSM analysis of the treated skin. In vivo antifungal activity on albino rats demonstrated vesicle based gel formulations to be safe, non irritant and more effective in topical treatment of fungal infections, with no drug reaching to systemic circulation. Thus, findings of the study demonstrate elastic liposomes and ethosomes, as a carrier are an attractive approach for enhanced topical delivery of Luliconazole.

Development and evaluation of a film-forming system hybridized with econazole-loaded nanostructured lipid carriers for enhanced antifungal activity against dermatophytes

Treatment of skin infection by dermatophytes is still limited, and the application of conventional topical formulations (ointments, creams, etc.) cause patient discomfort due to repeated administration and low efficacy. This study describes the film-forming system (FFS) hybridized with econazole (ECO)-loaded nanostructured lipid carriers (NLC) for enhanced antifungal activity against dermatophytes. We assumed that the application of NLC could effectively increase the skin permeability of ECO, thereby suppressing the growth of dermatophytes in stratum corneum as well as in epidermis. Meanwhile, ECO-NLC hybrid FFS (ECO-NLC@FFS) could increase the adhesion of ECO-NLC to the skin and prolong the antifungal activity of ECO. First, we optimized ECO-NLC, which shows nanosized particle (199 nm), high encapsulation efficiency (92.5%), and biocompatibility. ECO-NLC@FFS formed a transparent, homogeneous, and hard-to-remove film after topical application. In vitro skin permeation and deposition studies demonstrated that ECO-NLC@FFS showed 1.5-fold higher skin permeation and 3-fold higher ECO deposition in the epidermis layer than a commercial product, which resulted from the nanosized particle and its occlusion effect. And, ex vivo and in vivo antifungal activity studies confirmed that ECO-NLC@FFS improved the skin adhesion of ECO-NLC, thereby allowing ECO to be continuously exposed to the infection sited and reducing the number of applications with a single dose. These results showed that this hybrid system could be a potential for effectively improving the efficacy of antifungal agents and the patient compliance in the treatment of dermatophytes. Statement of significanceTreatment of skin infection by dermatophytes is difficult due to the inconvenience and low efficacy of conventional topical formulations. Here, we demonstrated the potential of a film-forming system (FFS) hybridized with nanostructured lipid carriers (NLC). First, we confirmed that the enhanced skin permeability of drug was improved by NLC. In addition, the hybridization of NLC with FFS improved the skin adhesion of NLC, allowing the drug to exhibit a sustained release profile and prolong antifungal activity. Given the maximized antifungal activity, this hybrid system can be used as a potential pharmaceutical technique to improve patient convenience and achieve complete treatment of skin infection.

Lopinavir Loaded Spray Dried Liposomes with Penetration Enhancers for Cytotoxic Activity.

HIV protease inhibitors (HIV-PI) are the drugs utilized for the treatment of HIV. However, their effectiveness is limited due to lack of bioavailability and they need to be coadministered with another drug. In this study single lopinavir (LPV) loaded phospholipid vesicles were prepared by the spray-drying method. The LPV-loaded spray-dried powder (L-SDP) was transformed into vesicles and then entrapped in a cream base with peppermint and olive oil. It is an Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) membrane fluidity study that is used to predict oil's effect on skin. The central composite design was used to optimize the L-SDP cream formulation. Ex-vivo drug release, skin deposition study, and cell proliferation assays were carried out using cancer cell lines of breast, lung, and skin melanoma. Analysis of DNA by flow cytometry on human breast cancer cell line MDA-MB-231 was carried out. The fluorescence microscopy, histopathological study, and in-vivo bioavailability studies were performed to measure the penetration and inertness of cream in animals. A membrane fluidity study revealed the effectiveness of oils as penetration enhancers. The L-SDP cream showed comparatively superior (%) drug deposition and permeability . Fluorescence images further confirm the penetration ability of the L-SDP cream which showed promising antiproliferative action on breast and lung cancer cells. The histopathological study demonstrates the inertness of cream while in-vivo bioavailability studies showed the many-fold increase in bioavailability of LPV. The liposomal drug delivery system of LPV has the potential to expose skin to systemic circulation and is useful for treating cancer.

Formulation of topical NLCs to target macrophages for cutaneousleishmaniasis

The present work aimed to synthesize drug loaded nanostructured lipid carriers (NLCs) for treatment of cutaneousleishmaniasis (CL). Topical drug delivery is a favourable option in treatment of localized cutaneousleishmaniasis (LCL) and is always considered superior over systemic therapy and intralesional antimony injections. Curcumin was chosen as model antileishmanial drug and drug loaded NLCs (Cur-NLCs) were prepared by hot homogenization followed by probe sonication technique. Prepared Cur-NLCs were characterized for particle size (312 ± 1.89 nm), encapsulation efficiency (88 ± 2.45%), zeta potential (−38 ± 0.93 mV) and Polydispersity index (0.305 ± 0.17). Blank and drug loaded NLCs were characterized for morphology using scanning electron microscopy (SEM) and FTIR was done to study any interaction between excipients. Cur-NLCs were also characterized for in vitro drug release and ex vivo skin permeation and deposition study. Moreover, targeting potential to macrophages and deeper skin layers was evaluated using fluorescence microscopy. A higher drug deposition in stratum corneum and deeper skin layers was achieved with Cur-NLCs gel as compared to curcumin reference gel (RG). The in vitro antileishmanial assay against promastigotes and axenic amastigote like cells (AALCs) demonstrated Cur-NLCs (IC50 values of 105 μg/ml and 190 μg/ml against promastigotes and AALCs respectively) to be superior as compared to plain curcumin solution (IC50 values of 165 μg/ml and 243 μg/ml against promastigotes and AALCs respectively). Results suggested that topical application of drug loaded NLCs can lead to targeted delivery of antileishmanial drugs to site of action i.e., infected macrophages residing in deeper skin layers.

Tailoring of PEGylated bilosomes for promoting the transdermal delivery of olmesartan medoxomil: in-vitro characterization, ex-vivo permeation and in-vivo assessment.

IntroductionThe intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into PEGylated bilosomes (PBs) for augmenting its transdermal delivery. PBs contain PEGylated single chain edge activator besides the components of traditional bilosomes (Span 60, cholesterol and bile salts). The PEG gives further resilience to vesicle membrane and is speculated to augment both permeability and bioavailability of OLM.MethodsA 24 factorial experiment was constructed to inspect the impact of diverse variables on vesicles’ features and sort out the optimal formula adopting Design Expert® software utilizing thin film hydration technique. Vesicles’ evaluation was done by finding out entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and amount of drug released after 6 hrs (Q6h). The optimal formula was selected and characterized for further investigations.ResultsThe optimal formula (PB15) showed spherical vesicles with EE% of 72.49±0.38%, PS of 559.30±10.70 nm, PDI of 0.57±0.15, ZP of −38.35±0.65 mV and Q6h of 59.60±0.24%. PB15 showed higher deformability index (28.39±5.71 g) compared to traditional bilosomes (5.88±0.90 g) and transethosomes (14.94±0.63 g). Further, PB15 showed superior skin permeation from rat’s skin relative to the drug suspension. Moreover, confocal laser scanning microscopy examination revealed efficient penetration of the fluoro-labeled PB15 through skin. Histopathological study ensured the safety of PB15. In addition, in-vivo skin deposition studies showed higher OLM deposition in rat’s skin from PB15 compared to transethosomes and OLM suspension. Furthermore, pharmacodynamic and pharmacokinetic studies performed using male Wistar rats and male Albino rabbits, respectively, showed the superiority of PB15 over oral tablets. PB15 was found to have significantly higher AUC0–48 and AUC0–∞ relative to the oral tablets. As well, the relative bioavailability of PB15 was found to be 235.04%.ConclusionOverall, the obtained results confirmed the creditable effect of PB15 for transdermal delivery.

Non-Propellant Foams of Green Nano-Silver and Sulfadiazine: Development and In Vivo Evaluation for Burn Wounds.

A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies. NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out. NPF was applied onto secondary thermal wounds manifested on mice models followed by macroscopic and histological examinations. NPF had an average globule size of <75nm. The viscosity was ~10cP indicating the feasibility of expulsion from the container upon actuation. With no skin irritation, the foams showed a higher skin deposition of SD. A high contraction and an evident regeneration of the skin tissue upon treatment with NPF indicated a good recovery from the thermal injury was apparent from the histology studies. NPF represents an alternative topical formulation that can be employed as a safe and effective treatment modality for superficial second degree (partial thickness) burn wounds. With a minimal requirement of mechanical force, the no-touch application of NPF makes it suitable for sensitive and irritant skin surfaces.

Development of MART for the Rapid Production of Nanostructured Lipid Carriers Loaded with All-Trans Retinoic Acid for Dermal Delivery.

All-trans retinoic acid (ATRA) has been regarded as a wonder drug for many dermatological complications; however, its application is limited due to the extreme irritation, and toxicity seen once it has sufficiently concentrated into the bloodstream from the skin. Thus, the present study was aimed to increase the entrapment of ATRA and minimize its transdermal permeation. ATRA incorporated within nanostructured lipid carriers (NLCs) were produced by a green and facile thin lipid-film based microwave-assisted rapid technique (MART). The optimization was carried out using the response surface methodology (RSM)-driven artificial neural network (ANN) coupled with genetic algorithm (GA). The liquid lipid and surfactants were seen to play a very crucial role culminating in the particle size (< 70nm), zeta potential (< - 32mV), and entrapment of ATRA (> 98%). ANN-GA-optimized NLCs required a minimal quantity of the surfactants, formed within 2min and were stable for 1year at different storage conditions. The optimized NLC-loaded creams showed a skin retention (ex vivo) to an extent of 87.42% with no detectable drug in the receptor fluid (24h) in comparison to the marketed cream which released 47.32% (12h) of ATRA. The results were in good correlation with the in vivo skin deposition studies. The NLCs were biocompatible and non-skin irritant based on the primary irritation index. In conclusion, the NLCs were seen to have a very high potential in overcoming the drawbacks of ATRA for dermal delivery and could be produced conveniently by the MART.

Formulation of topical ibuprofen solid lipid nanoparticle (SLN) gel using hot melt extrusion technique (HME) and determining its anti-inflammatory strength.

Solid lipid nanoparticles (SLN) have been formulated using various batch processes, e.g., solvent diffusion evaporation, emulsification solvent evaporation followed by size reduction using high-pressure homogenization (HPH) or ultrasonication. However, for the manufacturing of formulations, continuous processes are always preferred over batch processes since they are more efficient and offer better quality of the end product. Hence, we developed topical SLN of ibuprofen (IBU) using hot melt extrusion (HME), prepared a gel formulation, and performed its in vitro and in vivo evaluation. Effect of different variables of HME equipment and materials used in SLN was optimized using design of experiment (DoE) approach. Stable 0.48% IBU SLN with particle size 60.2 ± 4.81nm and entrapment efficiency 90.41 ± 3.46% were developed which further gelled using 1% carbopol 981A. Drug release study, skin deposition study, and in vivo anti-inflammatory activity studies showed 84.37 ± 4.65% drug release, 12.05 ± 0.81% drug deposition, and 40.17 ± 2.41% edema inhibition respectively in case of IBU SLN gel (IBU-SLN-G) which was significantly higher (p < 0.05) than control IBU gel (C-IBU-G) with 50.11 ± 0.57% drug release, 4.11 ± 1.10% deposition, and 20.08 ± 3.23% edema inhibition respectively. In conclusion, HME offers a single step process for manufacturing for SLN which avoids high stress particle size reduction techniques used for SLN preparation.

Optimization and Evaluation of Beclomethasone Dipropionate Micelles Incorporated into Biocompatible Hydrogel Using a Sub-Chronic Dermatitis Animal Model.

The current study is concerned with the development and characterization of mixed micelles intended for the dermal delivery of beclomethasone dipropionate, which is a topical corticosteroid used in the management of atopic dermatitis. Mixed micelles were prepared using thin-film hydration technique, employing different concentrations of pluronic L121 with either poloxamer P84 or pluronic F127 with different surfactant mixture-to-drug ratios. The prepared formulae were characterized concerning entrapment efficiency, particle size, and zeta potential. Two formulae were chosen for ex vivo skin deposition studies: one formulated using pluronic L121/poloxamer P84 mixture while the other using pluronic L121/pluronic F127 mixture. The optimum formula with the highest dermal deposition was subjected to morphological examination and was formulated as hydroxypropyl methylcellulose hydrogel. The hydrogel was evaluated regarding viscosity and was subjected to ex vivo deposition study in comparison with the commercially available cream Beclozone®. In vivo histopathological study was conducted for both the hydrogel and Beclozone® in order to evaluate their healing efficiency. In vivo histopathological study results showed that the prepared hydrogel successfully treated sub-chronic dermatitis in an animal model within a shorter period of time compared to Beclozone®, resulting in better patient compliance and fewer side effects.

Skin Targeting of Oxiconazole Nitrate Loaded Nanostructured Lipid- Carrier Gel for Fungal Infections.

The progression of fungal infections can be rapid and serious due to compromising with immune function. They may cause liver damage, affect estrogen levels or may cause allergic reactions. Oxiconazole nitrate (OXZN) is a broad spectrum commonly used antifungal drug. It acts by erogosterol biosynthesis inhibition, which causes lysis of the fungal cell membrane because of changes in both membrane integrity and fluidity and direct membrane damage of fungal cells. However, its poor water solubility and short half-life (3-5 h) limit its applications. This study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier (NLC) to improve its solubility and prolong its release for the treatment of fungal infection via topical administration. OXZN-NLC was prepared by ultrasonication method using 32 full factorial design. Glyceryl monostearate (GMS) (X1) and oleic acid (X2) were used as independent variables and particle size and percentage entrapment efficiency (% EE) as dependent variables. The OXZN-NLCs were characterized for particle size, particle morphology and entrapment efficiency. The mean diameter of optimized OXZN-NLCs was found to be 124 ± 2 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM). Skin deposition study showed about 82.74% deposition as compared with the marketed formulation that showed 68.42% deposition. The developed NLCs show a sustained release pattern and high drug disposition in the infected area. OXZN-NLC could be a potential alternative for the treatment of topical fungal infection after clinical evaluation in near future.

Implementing Central Composite Design for Developing Transdermal Diacerein-Loaded Niosomes: Ex vivo Permeation and In vivo Deposition.

Background: Niosomes are surfactant-based vesicular nanosystems that proved their efficien-cy in transdermal delivery by overcoming skin inherent anatomic barrier; startum corneum. Central com-posite design is an efficient tool for developing and optimizing niosomal formulations using fewer exper-iments.Objective: The objective of this study was to prepare niosomes as a transdermal delivery system of di-acerein using film hydration technique, employing central composite design, for avoiding its oral gastroin-testinal problems.Methods: Three-level three-factor central composite design was employed for attaining optimal niosomes formulation with the desired characteristics. Three formulation variables were assessed: amount of salt in hydration medium (X1), lipid amount (X2) and number of surfactant parts (X3). DCN-loaded niosomes were evaluated for entrapment efficiency percent (Y1), particle size (Y2), polydispersity index (Y3) and zeta potential (Y4). The suggested optimal niosomes were subjected to further characterization and utilized as a nucleus for developing elastic vesicles for comparative ex vivo and in vivo studies.Results: The values of the independent variables (X1, X2 and X3) in the optimal niosomes formulation were 0 g, 150 mg and 5 parts, respectively. It showed entrapment efficiency percentage of 95.63%, parti-cle size of 436.65 nm, polydispersity index of 0.47 and zeta potential of -38.80 mV. Results of ex vivo permeation and skin deposition studies showed enhanced skin permeation and retention capacity of the prepared vesicles than drug suspension.Conclusion: Results revealed that a transdermal niosomal system was successfully prepared and evaluat-ed using central composite design which will result in delivering diacerein efficiently, avoiding its oral problems.