Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
Int J Pharm. 2021 Jan 5;592:120016. doi: 10.1016/j.ijpharm.2020.120016. Epub 2020 Nov 8.
The concepts of mucoadhesion and mucoadhesive polymers were introduced in the 20th century, leading to several advantages. These included enhanced drug absorption and extended residence at specific site of action. Polymeric excipients underwent chemical modification with sulfhydryl groups on the polymeric backbone so as to improve mucoadhesive features as well as potential. This modification resulted in compounds mimicking the nature of secreted mucus glycoproteins. Thus, these thiol group-bearing excipients presented the ability to attach covalently to the mucosa by the disulfide bonding. Nevertheless, the first generation of these thiol-modified polymers, named thiomers, presented disadvantages such as low stability in aqueous media and/or the high susceptibility towards oxidation along with the drawback of low sufficient reactive functional moieties on the polymeric backbone at lower pH. Therefore, in the 21st century, a second generation of preactivated or S-protected polymers with protected thiol moieties were developed, as well as a third generation of thiomers, solving some of the previously described problems. This review article aimed to highlight the progess on a potent sulfhydryl modification during the last decades and the posterior characterization and in vitro/ex vivo/in vivo mucoadhesiveness.
黏膜黏附及黏膜黏附聚合物的概念于 20 世纪被提出，由此带来了若干优势。这些优势包括增强药物吸收和在特定作用部位的延长驻留。聚合物辅料通过在聚合物主链上引入巯基进行化学修饰，以改善黏膜黏附特性和潜力。这种修饰导致了模拟分泌黏液糖蛋白性质的化合物的产生。因此，这些带有巯基的辅料能够通过二硫键与黏膜发生共价结合。然而，第一代被称为硫醚的巯基修饰聚合物存在缺点，例如在水介质中的低稳定性和/或对氧化的高敏感性，以及在较低 pH 值时聚合物主链上反应性官能团数量不足的缺点。因此，在 21 世纪，开发了第二代预激活或 S 保护聚合物以及第三代硫醚，解决了之前描述的一些问题。本文旨在强调过去几十年中在有力的巯基修饰方面取得的进展，以及随后的表征和体外/体内/体内黏膜黏附性。
