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Based on the fact that the orifices, or infundibulum, that surround human hairs constitute only 0.1% of the total surface area of human skin,1 one might predict this route of penetration to be of minor importance. However, on places of the human body where hair density is much higher such as the face, this local surface area can be much higher—as much as 10%.2 Combine this with the fact that the skin barrier is not as strong in the infundibulum as it is on the surface of the skin (see Figure 1), and it becomes clear that this route of entry into the skin cannot be ignored. During early days of skin delivery, transfollicular delivery of chemicals into and through skin was investigated but one of the main difficulties was the validity of the models available to investigate this route of entry. Three basic methods were used to investigate transfollicular delivery:
1.In the early 1990s, Hueber et al. developed a method in which skin was artificially scarred, resulting in the absence of hair follicles and sebaceous glands, the thinning of collagenous fibers with parallel orientation to the dermo-epidermal junction, and a decrease in the number or disappearance of elastic fibers.4 The skin penetration of four steroids: progesterone, testosterone, estradiol and hydrocortisone, was investigated and their levels of penetration were found to be significantly higher (1.7 to 3.1-fold) in normal skin than in scarred skin. From this, the authors concluded that human skin appendages, i.e., hair follicles and sebaceous glands, constituted a route of penetration for steroids and, likely, other chemicals of similar molecular weight and properties.4
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