Abstract
In vitro permeation test (IVPT) is a critical part of the prescription screening and evaluation of topical/transdermal drug delivery system, 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. The 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 similar kinetic model fitting results to mini-porcine skin. The DSE has a better similarity to porcine skin compared to 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.
摘要體外滲透試驗（IVPT）是外用/透皮給藥系統(tǒng)處方篩選和評估的關鍵部分，一般采用體外人體皮膚或動物皮膚作為皮膜。由于倫理問題和真實皮膚的巨大變異性等問題，開發(fā)皮膚等效物來替代動物/人體皮膚具有很高的科學和工業(yè)價值。在此，我們開發(fā)了一種雙層皮膚等效物（DSE），它同時包含真皮模擬結構和表皮屏障功能。真皮結構由光交聯(lián)糖胺聚糖、海藻酸鈣和明膠組成；而表皮屏障模擬結構則是電紡納米聚氨酯膜。主要由于多糖和蛋白質復合材料的協(xié)同作用，形成的 DSE 具有與真實全層皮膚相似的壓縮模量。最重要的是，對于三種不同Log P的模型藥物，DSE與小豬皮具有很高的相關性和相似的透皮藥物釋放行為。與其他已報道的皮膚等效物相比，DSE 與豬皮膚的相似度更高。此外，DSE 的抗?jié)B透能力可通過調(diào)整配方來模擬不同類型的皮膚。
