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羧甲基茯苓聚糖-脱氧胆酸共轭物的自聚集纳米颗粒作为阿霉素的载体

Self-aggregated nanoparticles of carboxylic curdlan-deoxycholic acid conjugates as a carrier of doxorubicin.

作者信息

Yan Jing-Kun, Ma Hai-Le, Chen Xia, Pei Juan-Juan, Wang Zhen-Bin, Wu Jian-Yong

机构信息

The Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, Jiangsu, China; School of Food & Biological Engineering, Jiangsu University, Zhenjiang 212013, China.

School of Food & Biological Engineering, Jiangsu University, Zhenjiang 212013, China.

出版信息

Int J Biol Macromol. 2015 Jan;72:333-40. doi: 10.1016/j.ijbiomac.2014.08.035. Epub 2014 Sep 2.

Abstract

In this study, a new non-toxic, biodegradable, biocompatible and water-soluble carboxylic curdlan bearing the dissociable COOH group in 100% purity, which was prepared by 4-acetamido-TEMPO-mediated oxidation, was hydrophobically modified by deoxycholic acid (DOCA) to attain novel amphiphilic curdlan derivatives (CCDs) for the preparation of nano-carriers for antitumor drug doxorubicin (DOX). Under the effect of ultrasonication, the carboxylic curdlan derivatives in water were self-aggregated into spherical nanoparticles with diameters ranging from 214 nm to 380 nm. The critical aggregation concentrations decreased from 0.047 mg/mL to 0.016 mg/mL with increasing DS of DOCA. DOX-loaded CCD nanoparticles were prepared in an aqueous medium with dialysis method. The DOX-CCD nanoparticles exhibited pH- and dose-dependent drug release profiles during in vitro release experiments. Moreover, the drug transport mechanism was Fickian diffusion according to the Ritger-Peppas model. The CCD nanoparticles might be explored as potential carriers for hydrophobic drugs with controlled release and delivery functions.

摘要

在本研究中,通过4-乙酰氨基-TEMPO介导的氧化反应制备了一种新型的无毒、可生物降解、生物相容且水溶性的羧甲基化的可解离COOH基团的100%纯度的凝胶多糖,用脱氧胆酸(DOCA)对其进行疏水改性,以获得新型两亲性凝胶多糖衍生物(CCDs),用于制备抗肿瘤药物阿霉素(DOX)的纳米载体。在超声作用下,水中的羧甲基化凝胶多糖衍生物自聚集形成直径为214 nm至380 nm的球形纳米颗粒。随着DOCA取代度(DS)的增加,临界聚集浓度从0.047 mg/mL降至0.016 mg/mL。采用透析法在水介质中制备了载DOX的CCD纳米颗粒。在体外释放实验中,DOX-CCD纳米颗粒表现出pH和剂量依赖性的药物释放曲线。此外,根据Ritger-Peppas模型,药物转运机制为菲克扩散。CCD纳米颗粒有望作为具有控释和递送功能的疏水药物的潜在载体进行探索。

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