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一种微流控方法制备蔗糖修饰的脂质体,可增加乳腺癌细胞的摄取。

A microfluidic approach to fabricate sucrose decorated liposomes with increased uptake in breast cancer cells.

机构信息

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento, 6, 61029 Urbino, (PU), Italy.

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento, 6, 61029 Urbino, (PU), Italy.

出版信息

Eur J Pharm Biopharm. 2022 Sep;178:53-64. doi: 10.1016/j.ejpb.2022.07.015. Epub 2022 Jul 30.

Abstract

Developing targeted drug delivery systems is an urgent need to decrease the side effects and increase the drug's efficiency. Most cancer cells show an increased sugar consumption compared to healthy cells due to the deregulation of sugar transporters. Consequently, liposomes, as a biocompatible nanocarrier, could be surface decorated by sugars to enhance drug targeting into cancer cells. Our work outlines a new strategy to easily manufacture sucrose decorated liposomes using sucrose stearate, a biocompatible and biodegradable non-ionic surfactant, with a scalable microfluidic approach. Sucrose decorated liposomes were loaded with berberine hydrochloride, a well-known phytochemical compound to investigate its effects on triple-negative breast cancer cells (MDA-MB-231). Using the microfluidic manufacturing system, we prepared berberine-loaded liposomes using a mixture of phosphatidylcholine and cholesterol with and without sucrose stearate with a size up to 140 nm and narrow polydispersity. Stability was confirmed for 90 days, and the in vitro release profile was evaluated. The formulations showed acceptable in vitro biocompatibility and significantly higher anti-proliferative effect on MDA-MB-231 cell line. These results have been confirmed by an increased uptake evaluated by flow cytometry and confocal microscopy. Taken together, our findings represent an innovative, easy, and scalable approach to obtain sugar decorated liposomal formulations without any surface-chemistry reactions. They can be potentially used as an anticancer targeted drug delivery system.

摘要

开发靶向药物输送系统是降低副作用和提高药物效率的迫切需要。与健康细胞相比,大多数癌细胞由于糖转运蛋白的失调而显示出更高的糖消耗。因此,作为一种生物相容性的纳米载体,脂质体可以通过糖来表面修饰,以增强药物对癌细胞的靶向作用。我们的工作概述了一种使用蔗糖硬脂酸(一种生物相容和可生物降解的非离子表面活性剂)通过可扩展的微流控方法轻松制造蔗糖修饰脂质体的新策略。蔗糖修饰的脂质体被盐酸小檗碱(一种众所周知的植物化学化合物)装载,以研究其对三阴性乳腺癌细胞(MDA-MB-231)的作用。使用微流控制造系统,我们使用含有和不含有蔗糖硬脂酸的磷脂酰胆碱和胆固醇混合物制备了载有盐酸小檗碱的脂质体,其粒径高达 140nm 且具有较窄的多分散性。稳定性在 90 天内得到了确认,并评估了体外释放曲线。这些制剂表现出可接受的体外生物相容性,并且对 MDA-MB-231 细胞系的增殖抑制作用显著更高。这些结果通过流式细胞术和共聚焦显微镜评估的摄取增加得到了证实。总之,我们的研究结果代表了一种创新、简单且可扩展的方法,可以获得无需任何表面化学反应的糖修饰脂质体制剂。它们可能被用作抗癌靶向药物输送系统。

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