Polymeric micelles (PM) are extensively used to improve the delivery of hydrophobic drugs. Many different PM have been designed and evaluated over the years, and some of them have steadily progressed through clinical trials. Increasing evidence suggests, however, that for prolonged circulation times and for efficient EPR-mediated drug targeting to tumors and to sites of inflammation, PM need to be stabilized, to prevent premature disintegration. Core-crosslinking is among the most popular methods to improve the in vivo stability of PM, and a number of core-crosslinked polymeric micelles (CCPM) have demonstrated promising efficacy in animal models. The latter is particularly true for CCPM in which (pro-) drugs are covalently entrapped. This ensures proper drug retention in the micelles during systemic circulation, efficient drug delivery to pathological sites via EPR, and tailorable drug release kinetics at the target site. We here summarize recent advances in the CCPM field, addressing the chemistry involved in preparing them, their in vitro and in vivo performance, potential biomedical applications, and guidelines for efficient clinical translation.

中文翻译：

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核心交联聚合物胶束：原理、制备、生物医学应用和临床转化


聚合物胶束（PM）广泛用于改善疏水性药物的递送。多年来，人们已经设计和评估了许多不同的PM，其中一些已经通过临床试验稳步取得进展。然而，越来越多的证据表明，为了延长循环时间以及有效地将 EPR 介导的药物靶向肿瘤和炎症部位，PM 需要稳定，以防止过早崩解。核心交联是提高PM体内稳定性的最流行的方法之一，许多核心交联聚合物胶束（CCPM）已在动物模型中表现出良好的功效。后者对于 CCPM 来说尤其如此，其中（亲）药物被共价捕获。这确保了体循环期间药物在胶束中的适当保留，通过 EPR 将药物有效输送到病理部位，并在目标部位实现可定制的药物释放动力学。我们在这里总结了 CCPM 领域的最新进展，讨论了制备它们所涉及的化学、它们的体外和体内性能、潜在的生物医学应用以及有效临床转化的指南。