Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo: Ex vivo permeation and skin irritation studies

Patel, Hetal; Barot, Bhavesh S.; Parejiya, Punit B.; Shelat, Pragna K.; Shukla, Arunkumar

doi:10.1016/j.colsurfb.2012.08.011

Cited by 104 publications

(53 citation statements)

References 43 publications

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“…When comparing the permeation of CP from the three nanoparticles in dispersion to non-encapsulated CP in solution, a clear and significant reduction was seen by encapsulating the drug, as was desired. Compared to previous works on rat skin permeability of CP formulated in form of microemulsion, microemulsion-gel, and a marketed formulation, human skin permeability for CP was two to four times lower when compared to the ethanolic solution [41]. In the previously mentioned report, the authors observed greater CP permeability when CP was formulated in a microemulsion compared to the marketed formulation, but a significant decrease of permeation after increasing the viscosity of the medium.…”

Section: Skin Permeation Studycontrasting

confidence: 55%

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects

Mathes

Melero

Conrad

et al. 2016

Journal of Controlled Release

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The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid Clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeared to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient -2-drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatorybased skin/scalp diseases. Graphical Abstract AbbreviationsAA: Alopecia areata ANOVA: Analysis of variance CCT: capric/caprylic triglyceride CP: Clobetasol propionate

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Section: Skin Permeation Studycontrasting

confidence: 55%

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects

Mathes

Melero

Conrad

et al. 2016

Journal of Controlled Release

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“…The dispersion was stirred for 2-3 h. KP-SLN (equivalent to 2.5% w/w of KP) was incorporated into the gel base. It was stirred for 1 h, and pH was adjusted to 6.0 ± 0.06, using (1N) sodium hydroxide solution to obtain KP-SLN gel with adequate consistency suitable for topical application (Kumbhar et al, 2013;Patel et al, 2013).…”

Section: Preparation Of Kp-sln-based Topical Gel (Kp-sln Gel)mentioning

confidence: 99%

Topical ketoprofen nanogel: artificial neural network optimization, clustered bootstrap validation, and in vivo activity evaluation based on longitudinal dose response modeling

et al. 2016

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Objectives: This work aimed at investigating the potential of solid lipid nanoparticles (SLN) as carriers for topical delivery of Ketoprofen (KP); evaluating a novel technique incorporating Artificial Neural Network (ANN) and clustered bootstrap for optimization of KP-loaded SLN (KP-SLN); and demonstrating a longitudinal dose response (LDR) modeling-based approach to compare the activity of topical non-steroidal anti-inflammatory drug formulations. Methods: KP-SLN was fabricated by a modified emulsion/solvent evaporation method. BoxBehnken design was implemented to study the influence of glycerylpalmitostearate-to-KP ratio, Tween 80, and lecithin concentrations on particle size, entrapment efficiency, and amount of drug permeated through rat skin in 24 hours. Following clustered bootstrap ANN optimization, the optimized KP-SLN was incorporated into an aqueous gel and evaluated for rheology, in vitro release, permeability, skin irritation and in vivo activity using carrageenan-induced rat paw edema model and LDR mathematical model to analyze the time course of anti-inflammatory effect at various application durations. Results: Lipid-to-drug ratio of 7.85 ], Tween 80 of 1.27% [bootstrap 95%CI: 0.601-2.40%], and Lecithin of 0.263% [bootstrap 95%CI: 0.263-0.328%] were predicted to produce optimal characteristics. Compared with profenid Õ gel, the optimized KP-SLN gel exhibited slower release, faster permeability, better texture properties, greater efficacy, and similar potency. Conclusions: SLNs are safe and effective permeation enhancers. ANN coupled with clustered bootstrap is a useful method for finding optimal solutions and estimating uncertainty associated with them. LDR models allow mechanistic understanding of comparative in vivo performances of different topical formulations, and help design efficient dermatological bioequivalence assessment methods.

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“…Topical corticosteroids, first experienced in clinical practice in the early 1950s, are widely used for skin disorders that require steroid therapy for anti-inflammatory and immunosuppressive purposes; yet the adverse effects of steroids significantly limit their usage since long-term treatment is required in such diseases. 1,2 Due to skin atrophy, steroid acne, hypopigmentation, transepidermal water loss (TEWL) increase, epidermal thinning, and allergic contact dermatitis that may arise during treatment, the actual dose must be precisely adjusted so that the ratio of benefit/risk should be clearly identified. 3 The physicochemical characteristics of the drug, the type of vehicle, and the physiological conditions of the skin can significantly affect percutaneous absorption.…”

Section: Introductionmentioning

confidence: 99%

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

Özcan¹,

Azizoğlu²,

Şenyiğit³

et al. 2013

IJN

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Abstract:The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.

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Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo: Ex vivo permeation and skin irritation studies

Cited by 104 publications

References 43 publications

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects

Topical ketoprofen nanogel: artificial neural network optimization, clustered bootstrap validation, and in vivo activity evaluation based on longitudinal dose response modeling

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

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