The role of hair follicles in the percutaneous absorption of caffeine.
BACKGROUND
* 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].


CONCLUSIONS
* 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.


OBJECTIVE
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 spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.
Otberg
Nina
N
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Charité-Universitaetsmedizin, Berlin, Germany.
Patzelt
Alexa
A
Rasulev
Utkur
U
Hagemeister
Timo
T
Linscheid
Michael
M
Sinkgraven
Ronald
R
Sterry
Wolfram
W
Lademann
Jürgen
J
D000279:Administration, Cutaneous; D000328:Adult; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D018859:Hair Follicle / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D002110:Caffeine