Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, S/N - Trindade, Florianópolis, SC, 88040-900, Brazil.
Pharm Res. 2023 May;40(5):1209-1221. doi: 10.1007/s11095-023-03499-9. Epub 2023 Mar 23.
Ethical restrictions as well as practical or economic issues related to use of animal and human skin has been the main reason the growth in the number of investigations with alternative models. Reconstructed skin models, for example, have been useful to evaluate the in vitro toxicity of compounds; however, these models usually overestimate the amount of drug permeated due to impaired barrier properties. In this review, the performance of synthetic and biological skin models in transport studies was compared by considering two compounds with different physicochemical properties. The advantages and limitations of each skin model are discussed in detail. Although synthetic and reconstructed skin models have shown to be useful in the formulation optimization step, they present many limitations: (1) impaired barrier properties; (2) lack of follicular transport; (3) no metabolism in synthetic membranes; (4) differences in terms of lipid organization; (5) more affected by formulation constituents. Therefore, animal and human tissues should still be prioritized in drug transport studies until new advances in alternative models are achieved. Investigations of the impact of cell-culture conditions on skin formation, in turn, bring perspectives related to the development of unhealthy/injured skin models (an aspect that still deserves attention).
由于与使用动物和人体皮肤相关的伦理限制以及实际或经济问题，替代模型的研究数量不断增加。例如，重建皮肤模型已被用于评估化合物的体外毒性；然而，由于屏障功能受损，这些模型通常会高估药物渗透的量。在本综述中，通过考虑两种具有不同物理化学性质的化合物，比较了合成和生物皮肤模型在传输研究中的性能。详细讨论了每种皮肤模型的优缺点。尽管合成和重建皮肤模型在配方优化步骤中表现出有用性，但它们存在许多局限性：（1）屏障功能受损；（2）缺乏毛囊传输；（3）合成膜中无代谢；（4）脂质组织的差异；（5）受配方成分的影响更大。因此，在替代模型取得新进展之前，动物和人体组织仍应优先用于药物传输研究。细胞培养条件对皮肤形成影响的研究反过来又带来了与不健康/受损皮肤模型开发相关的前景（这一方面仍值得关注）。
