Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, P. R. China.
Drug Dev Ind Pharm. 2021 Jun;47(6):839-856. doi: 10.1080/03639045.2021.1934869. Epub 2021 Jun 24.
Despite a potential drug with multiple pharmacological activities, curcumin has disadvantages of the poor water solubility, rapid metabolism, low bioavailability, which considerably limit its clinical application. Currently, polymeric micelles (PMs) have gained widespread concern due to their advantageous physical and chemical properties, easy preparation, and biocompatibility. They can be used to improve drug solubility, prolong blood circulation time, and allow passive targeted drug delivery to tumor through enhanced penetration and retention effect. Moreover, studies focused on tumor microenvironment offer alternatives to design stimulus-responsive smart PMs based on low pH, high levels of glutathione, altered enzyme expression, increased reactive oxygen species production, and hypoxia. There are various external stimuli, such as light, ultrasound, and temperature. These endogenous/exogenous stimuli can be used for the research of intelligent micelles. Intelligent PMs can effectively load curcumin with improved solubility, and intelligently respond to release the drug at a controlled rate at targeted sites such as tumors to avoid early release, which markedly improves the bioavailability of curcumin. The present review is aimed to discuss and summarize recent developments in research of curcumin-loaded intelligent PMs based on endogenous and exogenous stimuli, and facilitates the development of novel delivery systems for future research.
尽管姜黄素具有多种药理学活性，但由于其水溶性差、代谢快、生物利用度低，其临床应用受到了极大的限制。目前，聚合物胶束（PMs）因其具有有利的物理化学性质、易于制备和生物相容性而受到广泛关注。它们可以用来提高药物的溶解度，延长血液循环时间，并通过增强渗透和保留效应使药物被动靶向递送至肿瘤。此外，针对肿瘤微环境的研究为设计基于低 pH 值、高谷胱甘肽水平、改变酶表达、增加活性氧产生和缺氧的刺激响应智能 PMs 提供了替代方案。有各种外部刺激，如光、超声和温度。这些内源性/外源性刺激可用于智能胶束的研究。智能 PMs 可以有效负载姜黄素，提高其溶解度，并智能响应，在肿瘤等靶向部位以受控的速率释放药物，避免早期释放，从而显著提高姜黄素的生物利用度。本综述旨在讨论和总结基于内源性和外源性刺激的载姜黄素智能 PMs 的最新研究进展，并为未来的研究促进新型给药系统的发展。
