Clinical and Experimental Dermatology

Biography

Biography: Bozena Michniak-Kohn

Abstract

Introductionrn Hair follicles are considered as alternative pathway for topical and transdermal delivery. They canrncontribute to absorption and uptake of large molecules and nanoparticles. Therefore, nanocarriers can potentially be an effective drug delivery system targeting at hair follicle-related diseases, such as acne and alopecia1. Adapalene is a third generation retinoid and a highly lipophilic drug (logP=8.2), which is commercially available in forms of topical gel and lotion for treatment of mild to moderate acne2. In these commercial products adapalene exists as microcrystals dispersed in the formulations. Skin irritation has been reported with topical adapalene products due to direct contact of adapalene microcrystals containing acid groups (-COOH) with stratum corneum (SC), as well as presence of alcohols and surfactants in the formulation3. We have developed a platform technology to encapsulate hydrophobic drugs in tyrosinederived nanospheres (TyroSphere) and to facilitate skin delivery4. In this study, the applicability of TyroSphere for targeted delivery of adapalene into hair follicles is assessed.rnrnrnExperimental methodsrnrnAdapalene was loaded in the TyroSphere according to a previously reported protocol4 and the finalrnformulation was in form of liquid dispersion or a gel. Adapalene loaded-nanosphere (Ada-TyroSphere)rndispersion were characterized for their particle size, particle morphology, drug-polymer binding efficiency, drug sebum/water and stratum corneum/water partition coefficients, and drug’s crystallinity. Adapalene aqueous solubility was measured in presence of different amount of surfactant and was compared with TyroSphere formulations. HPLC technique was used for all the quantification purposes. Skin distribution of adapalene formulated in TyroSphere (gel and suspension) and marketed lotion (Differin®) was examined on human cadaver and porcine ear skin. Fluorescent microscopy was used to visualize adapalene delivery to epidermis and hair follicles.rnrnResults and discussionrnrnThe average particle size of TyroSphere was approximately 70 nm (PDI<0.22), which is suitable forrnfollicular uptake. TyroSphere provided substantial enhancement in the solubility of adapalene in phosphate buffer saline (PBS) pH=7.4. In X-Ray diffraction diagram, the crystalline peaks of adapalene were absence in Ada-TyroSphere, suggesting absence of adapalene microcrystals. Sebaceous glands are part of pilosebaceous unit and they produce and secrete sebum into follicular orifice. In order to target hair follicles it is critical to understand drug/formulation partition properties into human sebum5. The average partition coefficient of adapalene -in form of Ada-TyroSphere in PBS- into sebum after 15 h was 39.5± 7.1, while this parameter for SC partitioning was 18.6±1.5.rnFollowing 12 h application of 0.5 ml Ada-TyroSphere aqueous dispersion (0.02% drug w/w) onrndermatomed human cadaver skin, adapalene extracted from epidermis was measured as 3.43±1.14 g/cm2, while 100 mg Differin® lotion (0.1% drug w/w) delivered 1.25±1.28 μg/cm2 of drug into the epidermis (n=8). Moreover, results of another permeation study on porcine skin showed that there was no significance difference in delivery of adapalene to SC among Ada-TyroSphere gel formulations (0.025 % drug w/w) and Differin® (0.1% drug w/w). Figure 1 depicts fluorescent images of porcine skin treated topically with Ada-TyroSphere for 24 h (blue fluorescence coming from adapalene). Clearly, adapalene was delivered to upper epidermal layers and hair follicles.rn