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糖基化聚合物纳米颗粒:解决血液相容性悖论的甜蜜策略。

Glucosylated polymeric nanoparticles: a sweetened approach against blood compatibility paradox.

机构信息

Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram 695012, Kerala, India.

出版信息

Colloids Surf B Biointerfaces. 2013 Aug 1;108:337-44. doi: 10.1016/j.colsurfb.2013.03.001. Epub 2013 Mar 15.

Abstract

Surface functionalization strategies in generating stealth nano-carriers have garnered considerable attention in pharmaceutical research. In this regard, our investigation reports on the preparation and evaluation of glucose decorated poly lactic-co-glycolic acid (PLGA) nanoparticles as blood compatible nanoparticulate drug delivery system, with enhanced cellular uptake. Terminal carboxylic acid groups on PLGA were modified with the amino group of glucosamine and nanoparticles were generated by modified solvent diffusion (nano-precipitation) technique. Detailed in vitro experiments were performed to evaluate the eminence of glucose functionalization over unmodified nanoparticles, in terms of their hemocompatibility and cellular uptake. Glucosylation was confirmed by NMR and FTIR spectroscopy; PLGA and modified particles had average size in the range of 125nm. Glucosylation was an effective strategy in reducing plasma protein adsorption, complement activation and platelet plugging of PLGA nanoparticles. PLGA and their glucose modified versions were quite compatible with the blood cells and were non-cytotoxic. Moreover the uptake behaviour of glucose modified PLGA nanoparticles were enhanced in comparison to standard PLGA nanoparticles as emphasized by the z stacking analysis following confocal imaging. Precisely the stealth properties of glucose modified PLGA nanoparticles (PLGA-Glu), with enhanced cellular internalization, seems to be a safe and efficient system for intravenous drug delivery applications.

摘要

在药物研究中,表面功能化策略在制备隐形纳米载体方面引起了相当大的关注。在这方面,我们报告了葡萄糖修饰的聚乳酸-共-羟基乙酸(PLGA)纳米粒作为具有增强细胞摄取能力的血液相容纳米粒药物传递系统的制备和评价。通过改良的溶剂扩散(纳米沉淀)技术,将 PLGA 上的末端羧酸基团与葡糖胺的氨基进行修饰,生成纳米粒。进行了详细的体外实验,以评估葡萄糖功能化相对于未修饰纳米粒在血液相容性和细胞摄取方面的卓越性能。通过 NMR 和 FTIR 光谱证实了葡糖基化;PLGA 和修饰后的颗粒平均粒径在 125nm 范围内。葡糖基化是一种有效的策略,可以减少 PLGA 纳米粒的血浆蛋白吸附、补体激活和血小板堵塞。PLGA 及其葡萄糖修饰版本与血细胞相容性良好,无细胞毒性。此外,与标准 PLGA 纳米粒相比,葡萄糖修饰 PLGA 纳米粒的摄取行为得到了增强,如共聚焦成像后的 z 堆叠分析所强调的那样。确切地说,具有增强细胞内化能力的葡萄糖修饰 PLGA 纳米粒(PLGA-Glu)具有良好的隐形特性,似乎是一种安全有效的静脉给药应用系统。

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