The role of hair follicles in the percutaneous absorption of caffeine

Abstract

What is already known about this subject • In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [1–3]. • In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [4]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems. • Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [5]. • Caffeine is frequently used in skin penetration experiments as a model for highly water‐soluble compounds. Occlusion [6] and skin thickness [7] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[1]. What this study adds • The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances. • We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo. • These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures. Aims The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans. Methods Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish‐wax‐mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance. Results Caffeine (3.75 ng ml−1) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml−1). Highest values (11.75 ng caffeine ml−1) were found 1 h after application when the follicles were open. Conclusions Our findings demonstrate that hair follicles are considerable weak spot...

Triggering of drug release of particles in hair follicles

“…There is evidence that molecules, being transported into the hair follicles, are able to pass the barrier of the hair follicles and thus reach the living cells. This was shown, e.g., for the penetration of caffeine [26] and minoxidil [27]. In these experiments, the hair follicles were artificially closed, enabling a clear differentiation between follicular and intercellular penetration [28].…”

DETERMINATION OF PERMEATION PATHWAY OF GENTAMICIN INTO PIG’S EAR SKIN

“…When the follicular orifices were closed, penetration of caffeine into the skin took longer time which was 20 minutes and lower blood caffeine concentration was measured. Hence, the study performed shows clear differences between intercellular and follicular drug permeation pathway in vivo 19 . This proves that follicular route is highly significant for the permeation of drugs.…”

“…This limitation however, can be overcome by peeling the skin or by surface skin stripping with cyanoacrylate tapes 27 . Besides that, the analysis instrumentation used for the study can be improved by using a new surface ionization mass spectrometry (SI/MS) technique, which is able to show clear differences between interfollicular and follicular penetration of a topically applied substance as compared to UV Spectrometry 19 . The calculated percentage showed 44.83 % differences between gentamicin permeation through plugged and non-plugged skin which was slightly significant.…”

Getting Under the skin: What is the Potential of the Transfollicular Route in Drug delivery?

“…A further proof of the central role of HF for transdermal delivery is that the skin permeation of drugs depends on the site of application and is correlated with the HF density [4]. Highly relevant data were provided also by a study with healthy volunteers using blockage of HF openings [5]. The rationale for drug delivery via the HF is the large contact area and the large storage volume of the HF.…”