Differential stripping: introduction of a method to show the penetration of topically applied antifungal substances into the hair follicles

Abstract

Investigations concerning the penetration of topically applied drugs are the subject of a multiplicity of research, as the exact knowledge of these mechanisms is the prerequisite for the optimization of such substances. As the hair follicles represent a good long-term reservoir for topically applied substances, it can be assumed that they also represent a reservoir for microorganisms residing on and in the skin. Therefore, the hair follicles must be seen as one main site of action for antimicrobial substances and a simple non-invasive in vivo method for the determination of penetration of antimicrobial substances into the hair follicles. The aim of the present study was to show that differential stripping, by removing the hair follicle content selectively, represents a suitable method to demonstrate the penetration of antifungal substances into the hair follicles. The follicular casts, removed from skin areas of human volunteers, which were partially pre-treated with brilliant green (well-known antifungal properties), were applied on agar plates inoculated with Candida albicans. The results showed inhibited growth of C. albicans, if the follicular casts were removed from skin areas pre-treated with brilliant green. This indicates clear evidence that brilliant green had penetrated into the hair follicles. Therefore, differential stripping represents a suitable method to determine the penetration of antifungal substances into the hair follicles, which is of clinical importance for the optimization of topical antifungal therapeutics.

Targeting to the hair follicles: Current status and potential

“…Differential stripping allows us to selectively determine the amount of topically applied substance that penetrates into the hair follicles. The method combines the tape-stripping technique (removing the stratum corneum layer by layer), followed by cyanoacrylate skin surface biopsies (removing the content of the follicular infundibulum, the ''follicular cast'' consisting of a mixture of keratinized material, cell detritus, lipids and bacteria) [17,[26][27][28].…”

“…Examples of active substances examined for their follicular penetration include: minoxidil [32][33][34], plasmid DNA encoding IL1ra [34]; finasteride, cimetidine, melanin [35,36]; anti-androgen RU58841-myristate [37], hydrocortisone, testosterone [36,38]; titanium dioxide [8,25]; chemical UV filter (Eusolex 6300) [25]; curcumin [25,39]; inulin [40]; caffeine, nifluminic acid, paminobenzoic acid [7,9]; brilliant green [26], podophyllotoxin [30], estradiol, corticosterone, aldosterone, deoxyadenosine, adenosine [36], a-interferon, cyclosporin-A [41].…”

Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

“…The hair follicle is a reservoir for penetrated substances [2], and thus procedures to enhance this penetration pathway are valuable tools in dermatopharmaceutic research. Differential stripping methods have been widely used for investigations into the penetration of topically applied substances [3,4] and have even been proposed as methods to enhance penetration, e.g., in transcutaneous vaccination. With regard to hair follicle penetration cyanoacrylate skin surface stripping (CSSS), a variation of stripping using cyanoacrylate-based resins, is of special interest.…”

Follicular Penetration of Caffeine from Topically Applied Nanoemulsion Formulations Containing Penetration Enhancers: In vitro Human Skin Studies

“…In this study we focused on the contribution of transfollicular transport to skin permeation enhancement. To facilitate this investigation, we developed methods to separately determine the skin and follicular distribution of caffeine applied in a range of formulations, based on the previously reported methods of Lademann and his group [5,22]. We also developed a method to modify the hair follicles by selectively opening and blocking them, allowing them to be compared to untreated hair follicles in human skin.…”