Role of Transepidermal and Transfollicular Routes in Percutaneous Absorption of Steroids: In vitro Studies on Human Skin

Abstract

Percutaneous absorption theoretically comprises two components: the transepidermal and the transfollicular routes. The aim of the present work was to confirm this hypothesis in the human skin by comparing the in vitro percutaneous absorption of four steroids through scar skin without hair follicles and sebaceous glands and through normal adjacent skin from abdominal or mammary plasties. In all cases, the absorption of the four steroids was significantly higher in normal skin than in scar skin. The cumulative percentages of progesterone and testosterone after 8 h of application were, respectively, 3.1- and 2.4-fold higher in normal skin than in scar skin. After 24 h of application, the cumulative percentages of estradiol and hydro-cortisone were 1.7- and 2.4-fold higher in normal skin than in scar skin. At the end of the experiments, the quantities of drugs remaining in the skin after 8 or 24 h of application were the same in normal skin and in scar skin except for progesterone for which they were 2-fold greater in normal than in scar skin. In each case, a histological characterization of the scar skin was made in comparison with the normal adjacent skin. The main modifications observed on scar skin were the following: absence of hair follicles and sebaceous glands, thinning of the collagenous fibers with parallel orientation to the dermoepidermal junction and decrease in the number or disappearance of the elastic fibers. These experiments confirmed that human skin appendages, hair follicles and sebaceous glands, constitute a route of penetration for steroids and thus probably for other chemicals of similar molecular weight and properties.

Effect of Thermodynamic Activity on Skin Permeation and Skin Concentration of Triamcinolone Acetonide

“…In the literature, a major contribution of hair follicles to the skin permeation of steroids has already been reported. [16][17][18] Next, the hairless rat skin surface was observed in a SEM after application of a TA suspended solution at a concentration of 1000 mg/ml. As shown in the two pictures in Fig.…”

Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

“…The rate-limiting factor for skin absorption of ovarian corticosteroids may be related to the individual transport and metabolism differences in the skin and its appendages. 12,14 This study has demonstrated that progesterone is absorbed through the skin and that luteal levels of serum progesterone can be achieved. It appears that the progesterone cream used in this study may be a reasonable delivery system for elevating progesterone in postmenopausal women and thus for managing part or possibly all symptoms of ovarian corticosteroid deficiency.…”

“…A role for both the stratum corneum and the hair follicle has been proposed to influence the absorption rate. 12 Progesterone gel has been found to be absorbed rapidly and dose-dependently, with luteal phase concentrations achieved. In that study at 2-to 3-hour time points, a 100-mg dose resulted in peak levels of 5.9 to 8.0 ng/mL progesterone, although a lower 30-mg dose failed to raise progesterone to luteal levels.…”

Chemically Defined Protein-Free in vitro Culture of Mammalian Embryo Does Not Restrict Its Developmental Potential for Differentiation of Skin Appendages

“…Nevertheless, transepidermal and transfollicular routes in percutaneous absorption of substances have been described [Hueber et al, 1994]. Dermal exposure to substances during pregnancy has been reported to produce teratological effects in the offspring and genetic damage in the germ cells of treated males [Gutierrez-Espeleta et al, 1992] but has also been used as the route for the in vivo transfer of genes in rodent fetuses [Hayashi et al, 1996].…”