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仿生黏蛋白修饰的 PLGA 纳米粒增强血液相容性。

Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility.

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

J Colloid Interface Sci. 2013 Nov 1;409:237-44. doi: 10.1016/j.jcis.2013.07.004. Epub 2013 Jul 20.

Abstract

Efforts to develop long circulating polymeric nanoparticles have propelled many strategies in nanoparticle surface modification to bypass immune surveillance and systemic clearance. In this context, our present study reports on the preparation and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA) nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery system. Amino groups of mucin were conjugated to the terminal carboxylic acid groups on PLGA to be followed by nanoparticle synthesis via standard solvent evaporation technique. Detailed in vitro experiments were performed to illustrate the significance of alternating copolymer structured mucin modified PLGA nanoparticles in terms of enhanced hemocompatibility and cellular uptake. Mucylation proved promising in controlling PLGA nanoparticle- interaction with plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity and complement activation. Besides hemocompatibility, the modified and unmodified nanoparticles were also found to be cytocompatible with L929 and C6 cell lines. The fluorescent and confocal image analysis evaluated the extent of cellular uptake of nanoparticles into C6 cells. Specifically the combination of stealth properties and cellular internalization capacity of mucin modified PLGA nanoparticle (PLGA-Mucin) lead us to propose it as a safe, efficient and multifunctional nanoplatform for disease specific intravenous drug delivery applications as far as in vitro experiments are concerned.

摘要

为了开发长循环聚合物纳米粒,人们提出了许多纳米粒表面修饰策略,以逃避免疫监视和全身清除。在这种情况下,本研究报告了粘蛋白功能化聚乳酸-共-羟基乙酸(PLGA)纳米粒的制备和评价,作为具有血液相容性和细胞穿透性的纳米粒药物传递系统。粘蛋白的氨基与 PLGA 末端羧酸基缀合,然后通过标准溶剂蒸发技术合成纳米粒。进行了详细的体外实验,以说明交替共聚物结构粘蛋白修饰的 PLGA 纳米粒在增强血液相容性和细胞摄取方面的意义。粘蛋白化有望通过控制 PLGA 纳米粒与血浆蛋白(调理素)和血液成分的相互作用,通过溶血、血栓形成和补体激活来控制。除了血液相容性外,修饰和未修饰的纳米粒也被发现与 L929 和 C6 细胞系具有细胞相容性。荧光和共聚焦图像分析评估了纳米粒进入 C6 细胞的细胞摄取程度。具体来说,粘蛋白修饰的 PLGA 纳米粒(PLGA-Mucin)的隐身特性和细胞内化能力的结合,使我们提出将其作为一种安全、高效和多功能的纳米平台,用于疾病特异性静脉药物输送应用,就体外实验而言。

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