pH值响应聚乙二醇化壳聚糖基隐形纳米胶束的制备及其载药性能

doi:10.16085/j.issn.1000-6613.2015.01.030

化工进展 ›› 2015, Vol. 34 ›› Issue (1): 173-177,223.DOI: 10.16085/j.issn.1000-6613.2015.01.030

pH值响应聚乙二醇化壳聚糖基隐形纳米胶束的制备及其载药性能

姚文杰, 辛梅华, 李明春, 方江海

华侨大学材料科学与工程学院, 环境友好功能材料教育部工程研究中心, 福建厦门 361021

收稿日期:2014-05-19 修回日期:2014-06-15 出版日期:2015-01-05 发布日期:2015-01-05
通讯作者: 李明春,教授,博士生导师,研究方向为功能高分子材料研究。E-mail mcli@hqu.edu.cn。
作者简介:姚文杰(1987－),男,硕士研究生。
基金资助:
福建省重点科技项目(2009H0030)、福建省自然科学基金(2011J01312和2012J01396)及科技部科技人员服务企业(2009GJC40030)项目。

pH-responsive PEGylated nanoparticles based on dilauryl chitosan:Preparation,physicochemical characterization and in vitro evaluation

YAO Wenjie, XIN Meihua, LI Mingchun, FANG Jianghai

School of Material Science and Engineering, Huaqiao University, Engineering Research Center of Environment-Friendly Functional Materials, Ministry of Education, Xiamen 361021, Fujian, China

Received:2014-05-19 Revised:2014-06-15 Online:2015-01-05 Published:2015-01-05

摘要/Abstract

摘要： 聚乙二醇单甲醚(mPEG)先经过氯乙酸羧化后,再通过酰化反应接枝到双烷基壳聚糖上,制备高接枝度的N,N-双十二烷基-3,6-O-mPEG-壳聚糖(PEDLCS)双亲性衍生物,用¹H NMR、FTIR、EA等对产物进行表征,并用透析法制得PEDLCS载酮洛芬(KP)胶束。结果表明,PEDLCS在水溶液中能自组装形成胶束,CMC值为0.1170mg/mL;载药胶束的最优投料比为KP/PEDLCS=0.8:1,载药量34.48%,包封率65.78%,粒径155.1nm,Zeta电位-31.6mV。载药胶束在不同pH值条件下的响应性实验表明,随着pH值的减小,胶束的稳定性降低,胶束粒径变大,具有可逆性。pH值响应范围符合肿瘤细胞微环境(pH值为7.2～6.0),有望成为具有pH值响应主动靶向的隐形纳米胶束。

关键词: 两亲性壳聚糖, 聚乙二醇单甲醚, pH值响应性, 自组装胶束

Abstract: Through acylation reaction, a novel chitosan amphiphilic derivative, N, N-dilauryl- 3, 6-O-mPEG-chitosan (PEDLCS) with high degree of grafting was synthesized by grafting mPEG-COOH onto N, N-dilauryl chitosan. The product was characterized with¹H NMR, FTIR, and EA. KP-loaded PEDLCS micelles were prepared by dialysis. PEDLCS could form micelles via self-assembly in aqueous solution and the CMC value of PEDLCS was 0.1170 mg/mL. The drug loading content and efficiency of KP-loaded PEDLCS micelles were determined as 34.48% and 65.78% respectively under the optimal ratio of KP and PEDLCS (0.8:1). The KP-loaded PEDLCS micelles had average size of 155.1nm and zeta potential of -31.6 mV. The response experiments about drug-loaded micelle under the conditions of different pH values showed that stability of the micelles decreased and diameter of the micelles increased with decreasing pH value, and the process was reversible. The range of pH response rightly agreed with the growth microenvironment of tumor cell (pH7.2—6.0). It would be expected to become a new material of drug delivery system.

Key words: amphiphilic chitosan, mPEG, pH-responsive, self-assembly micelles

中图分类号:

O636.1

姚文杰, 辛梅华, 李明春, 方江海. pH值响应聚乙二醇化壳聚糖基隐形纳米胶束的制备及其载药性能[J]. 化工进展, 2015, 34(1): 173-177,223.

YAO Wenjie, XIN Meihua, LI Mingchun, FANG Jianghai. pH-responsive PEGylated nanoparticles based on dilauryl chitosan:Preparation,physicochemical characterization and in vitro evaluation[J]. Chemical Industry and Engineering Progree, 2015, 34(1): 173-177,223.

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pH值响应聚乙二醇化壳聚糖基隐形纳米胶束的制备及其载药性能

pH-responsive PEGylated nanoparticles based on dilauryl chitosan:Preparation,physicochemical characterization and in vitro evaluation

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