Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 N Charles St., Baltimore, MD 21218, USA.
Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, 1800 Orleans St., Baltimore, MD 21287, USA.
Adv Drug Deliv Rev. 2022 Dec;191:114543. doi: 10.1016/j.addr.2022.114543. Epub 2022 Oct 5.
Vaginal drug delivery systems are often preferred for treating a variety of diseases and conditions of the female reproductive tract (FRT), as delivery can be more targeted with less systemic side effects. However, there are many anatomical and biological barriers to effective treatment via the vaginal route. Further, biocompatibility with the local tissue and microbial microenvironment is desired. A variety of in vitro and ex vivo models are described herein for evaluating the physicochemical properties and toxicity profile of vaginal drug delivery systems. Deciding whether to utilize organoids in vitro or fresh human cervicovaginal mucus ex vivo requires careful consideration of the intended use and the formulation characteristics. Optimally, in vitro and ex vivo experimentation will inform or predict in vivo performance, and examples are given that describe utilization of a range of methods from in vitro to in vivo. Lastly, we highlight more advanced model systems for other mucosa as inspiration for the future in model development for the FRT.
阴道给药系统通常更适合治疗女性生殖道(FRT)的多种疾病和病症,因为通过阴道给药可以更有针对性,且全身副作用更小。然而,通过阴道途径进行有效治疗存在许多解剖学和生物学障碍。此外,还需要与局部组织和微生物微环境具有生物相容性。本文介绍了多种用于评估阴道给药系统理化性质和毒性特征的体外和离体模型。决定是否在体外使用类器官或离体新鲜人宫颈阴道黏液,需要仔细考虑预期用途和制剂特性。最理想的情况是,体外和离体实验将为体内性能提供信息或预测,并且给出了描述从体外到体内使用一系列方法的实例。最后,我们强调了其他黏膜的更先进模型系统,为 FRT 的未来模型开发提供灵感。