Double-layer skin equivalents as diffusion models for topical and transdermal drug delivery studies

Abstract

In vitro permeation test (IVPT) is a critical part of the prescription screening and evaluation of topical/transdermal drug delivery systems, in which ex vivo human skin or animal skin are generally used as skin membranes. The development of skin equivalents to replace animal/ human skins has high scientific and industrial value owing to the issues such as ethical issues and large variability of real skin. Here, a double-layer skin equivalent (DSE) containing both dermal-simulating structure and epidermal barrier function was developed. The dermal structure was composed of photo-crosslinked glycosaminoglycan, calcium alginate and gelatin; while the epidermal barrier-simulating structure was an electrospun nano-polyurethane-membrane. Mainly contributed to the synergistic effect of polysaccharide and protein composites, the formed DSE had similar compression modulus to that of real full-layer skin. Most of all it exhibited high correlation and similar transdermal drug release behavior with mini-porcine skin for three model drugs with different Log P. The DSE also showed comparable kinetic model fitting results to mini-porcine skin and exhibited a closer resemblance to porcine skin than other skin equivalents reported. Moreover, the penetration resisting ability of the DSE can be adjusted by adjusting the formulation to simulate different types of skin.