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羧甲基葡聚糖和壳聚糖的纳米聚电解质复合物提高壳聚糖介导的 miR-145 递送。

Nano polyelectrolyte complexes of carboxymethyl dextran and chitosan to improve chitosan-mediated delivery of miR-145.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.

Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Carbohydr Polym. 2017 Mar 1;159:66-75. doi: 10.1016/j.carbpol.2016.11.067. Epub 2016 Nov 24.

DOI:10.1016/j.carbpol.2016.11.067
PMID:28038755
Abstract

Chitosan (Ch) nanoparticles have emerged as a promising vector for gene delivery, nonetheless slow dissociation rate of the nanoparticles in cytoplasm is a drawback of using Ch. Herein, the Ch-mediated gene delivery was improved using PECs of Ch and carboxymethyl dextran (CMD) to transfer the micro RNA-145 (miR-145). The optimized nano PEC preparation method and effects of Ch molecular weight (Mw) and a CMD to Ch molar ratio (CMD:Ch) on physical characteristics and in vitro efficacy of the nano PECs was determined. The size of the nano PECs depended on the preparation method, Ch Mw, and CMD:Ch ratio. Also, the Ch Mw and CMD:Ch affected stability of the miR-145 PECs in presence of heparin. In vitro tests indicated the different gene transfection efficiency of the nano PECs with various compositions. As a novel vector, these nano PECs have excellent promise for gene delivery with an adequate balance between a complex stability and dissociation rate.

摘要

壳聚糖(Ch)纳米粒子已成为基因传递的一种有前途的载体,但纳米粒子在细胞质中解离速度缓慢是使用 Ch 的一个缺点。本文通过壳聚糖和羧甲基葡聚糖(CMD)的PEC 来传递 micro RNA-145(miR-145),改善了 Ch 介导的基因传递。优化了纳米 PEC 的制备方法,并确定了 Ch 分子量(Mw)和 CMD 与 Ch 摩尔比(CMD:Ch)对纳米 PEC 的物理特性和体外疗效的影响。纳米 PEC 的大小取决于制备方法、Ch Mw 和 CMD:Ch 比。此外,Ch Mw 和 CMD:Ch 影响了 miR-145 PEC 在肝素存在下的稳定性。体外试验表明,不同组成的纳米 PEC 具有不同的基因转染效率。作为一种新型载体,这些纳米 PEC 具有良好的基因传递前景,在复杂的稳定性和解离速度之间达到了适当的平衡。

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