双层皮肤等效物作为局部皮肤和透皮给药扩散实验模型的研究

2025-03-01 11:35:53 295阅读次数

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Runze Zhou a, 1, Zhi Xiao a, 1, Tianchi Lu a, b, Yaqi Zhang a, Ting Liu c, Liping Hu d, Xing Lu e, Feifei Wangf, Luyong Zhang c, *, Huixia Lv a, *

a Department of Pharmaceutics, China Pharmaceutical University, Nanjing 211198, China

b Qian Zhao Xin Ye Biotechnology, Beijing, 100091, China

c National Institutes for Food and Drug Control, Beijing 102629, China

d APAC Toxicology and Clinical Safety, Johnson and Johnson China Ltd., Shanghai, 200245, China

e Guangdong Biocell Biotechnology Co. Ltd., Xi’an, 710025, China

f Yunnan Yunke Characteristic Plant Extraction Laboratory Co. Ltd, Kunming, Yunnan 650106, China

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

体外渗透试验（IVPT）是外用/透皮给药系统处方筛选和评估的关键部分，一般采用体外人体皮肤或动物皮肤作为皮膜。由于伦理问题和真实皮肤的巨大变异性等问题，开发皮肤等效物来替代动物/人体皮肤具有很高的科学和工业价值。在此，我们开发了一种双层皮肤等效物（DSE），它同时包含真皮模拟结构和表皮屏障功能。真皮结构由光交联糖胺聚糖、海藻酸钙和明胶组成；而表皮屏障模拟结构则是电纺纳米聚氨酯膜。主要由于多糖和蛋白质复合材料的协同作用，形成的 DSE 具有与真实全层皮肤相似的压缩模量。最重要的是，对于三种不同Log P的模型药物，DSE与小猪皮具有很高的相关性和相似的透皮药物释放行为。与其他已报道的皮肤等效物相比，DSE 与猪皮肤的相似度更高。此外，DSE 的抗渗透能力可通过调整配方来模拟不同类型的皮肤。