A. Teichmann

Hair follicles - a long-term reservoir for drug delivery.

Nanoparticles represent an important drug carrier system. Recently, we have reported on the penetration and storage behavior of particular and non-particular substances revealing the superiority of particular substances in the range of 300–400 nm. In this regard, it was assumed that the rigid hair shaft acts as a geared pump, moving the particles deeper into the hair follicle. In the present investigation, the storage reservoir capacity of the stratum corneum and the hair follicle infundibulum and canal are compared. Interestingly, we could demonstrate a 10 times longer storage within the hair follicles. These results underscore the importance of the hair follicle for drug delivery purposes, mainly highlighting new possibilities for the future concerning retarded delivery, application frequency, and galenic design.

Application of optical non‐invasive methods in skin physiology: a comparison of laser scanning microscopy and optical coherent tomography with histological analysis

Background/purpose: Optical, non‐invasive methods, such as fluorescence laser scanning microscopy (LSM) and optical coherent tomography (OCT), have become efficient tools for the characterization of the skin structure in vivo, as well as real‐time investigation of distribution and penetration of topically applied substances.

Follicular Penetration: Development of a Method to Block the Follicles Selectively against the Penetration of Topically Applied Substances

Investigations into the penetration pathways of topically applied substances through the skin play an important role in dermatological science. Recently, the hair follicles have increasingly been recognized as an important pathway for percutaneous penetration, although the role of the follicles has still not been clarified in detail. Therefore, the aim of the present study was to develop an in vivo method for the analysis of the follicular rate of penetration processes. In order to reach this goal, the follicles were excluded from the penetration process of topically applied substances. Different study designs were evaluated, and we were able to show that the application of nail varnish to each follicular orifice represents an effective method of blocking the follicles selectively against the penetration of topically applied substances. In dermatological science, there is new information on the physiology of skin penetration processes, thus allowing examination of the follicular rate of penetration and improvement of the pharmacokinetics of topically applied substances.

Follicular Penetration of Topically Applied Caffeine via a Shampoo Formulation

Aims: Follicular drug delivery is the prerequisite for an effective treatment of androgenetic alopecia or other reasons of premature hair loss. Methods: The follicular penetration of caffeine, applied topically in a shampoo formulation for 2 min, was measured with highly sensitive surface ionization in combination with mass spectroscopy, a selective method for the detection of very small quantities of transcutaneously absorbed substances in the blood. An experimental protocol, developed to selectively block the follicular pathway within the test area, was used. Based on this principle, a clear distinction between interfollicular and follicular penetration of topically applied caffeine was feasible. Results: After 2 min, caffeine penetrated via the hair follicles and stratum corneum. Conclusion: It was found that the penetration via hair follicles was faster and higher compared with the interfollicular route and that hair follicles are the only pathway for fast caffeine absorption during the first 20 min after application.

Investigation of differences in follicular penetration of particle- and nonparticle-containing emulsions by laser scanning microscopy

Hair follicles represent a long-term storage of topically applied drugs and cosmetics in the skin. Analyzing the penetration of particle-and nonparticle-containing formulations by laser scanning microscopy, it was found, surprisingly, that particles at a size similar to the thickness of the keratin cells of the hair penetrate more efficiently into the hair follicles. These results were obtained from in vitro and in vivo investigations. It seems that the moving hairs in the follicles act as a geared pump because of the zigzag structure of the surface of the hairs. This pumping effect probably pushes particles with the corresponding size deep into the hair follicles.

An in vivo model to evaluate the efficacy of barrier creams on the level of skin penetration of chemicals

The reservoir function and the barrier function are important properties of the skin. The reservoir function is dependent on the barrier function which, however, needs support by protective measures, in particular under working conditions. Barrier creams represent a possibility to protect the skin.

Semiquantitative Determination of the Penetration of a Fluorescent Hydrogel Formulation into the Hair Follicle with and without Follicular Closure by Microparticles by Means of Differential Stripping

Recently, hair follicles were shown to be of great importance concerning the penetration and reservoir behavior of topically applied substances. Especially microparticles are known to be efficient drug carriers into the hair follicles. It has been shown in various investigations that, depending on their size, microparticles can be utilized to enhance the penetration of substances into the hair follicles. In the present study, it was investigated whether they could also be used to block the hair follicles to stop penetration. For this purpose, the follicular penetration of a sodium fluorescein-containing hydrogel and follicular reservoir depletion were investigated by means of differential stripping in vivo. In a second study design, the skin areas were pretreated with microparticles 5 µm in diameter. Subsequently, the follicular penetration of sodium fluorescein-containing hydrogel was likewise investigated by differential stripping. The results showed that the hair follicle infundibula contained a significant fluorescent signal when sodium fluorescein in hydrogel was applied. In contrast, in the case of pretreatment with microparticles, only a very low fluorescence signal was measurable in the hair follicle infundibula. The microparticles clearly blocked the follicular orifices so that a penetration of sodium fluorescein was almost completely inhibited. This was confirmed by histological investigations. Thus, depending on their size, microparticles act as efficient drug carriers or can be utilized as follicle blockers to stop the penetration of topically applied substances. This could be very useful in skin protection to prevent the storage of harmful topically applied substances in the hair follicles, known to represent long-term reservoirs.

Reservoir Function of the Stratum corneum: Development of an in vivo Method to Quantitatively Determine the Stratum corneum Reservoir for Topically Applied Substances

Investigations on the stratum corneum (SC) reservoir for topically applied substances are of importance in dermatologic science in order to assess the pharmacokinetics of these substances. In the present study, an in vivo method was developed to determine the SC reservoir quantitatively and to investigate the temporal behavior of this reservoir. Therefore, increasing amounts of an oil-in-water emulsion (o/w emulsion) containing 4% of a chemical UV filter were topically applied onto the flexor forearms of 5 healthy volunteers. The saturation of the SC reservoir was determined utilizing the tape stripping technique 1 and 6 h after application. The capacity of the SC reservoir for the o/w emulsion was found to be approximately 2.7 mg/cm2. Furthermore, a correlation of the capacity of the SC with transepidermal water loss was observed. Extending the time between the topical application and SC removal did not affect the distribution or the recovery rate of the UV filter in the SC. The results indicate that the reservoir of the SC is limited. This is reflected by the saturation level, which depends on the individual volunteer and, presumably, the topically applied substances and formulations used. The results show that the method developed is suited to quantitatively determine in vivo the SC reservoir for topically applied substances.

Penetration of microparticles into human skin

The efficacy of the penetration of microparticles into the human skin depends on the size and the type of the formulation with which they are topically applied. Microparticles with a diameter of >1 microm barely penetrate into the human skin. They are located on the skin surface and form a film which, for instance, can be used for camouflage or protection against UV radiation in sunscreens. While the penetration of the microparticles in the lipid layers of the stratum corneum is limited, they penetrate efficiently into the hair follicles up to a depth >2 mm, providing their diameter is <1.5 microm. Thus, microparticles can be used for drug delivery into the hair follicles.

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

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.