Stearic acid grafted chitosan oligosaccharide micelle as a promising vector for gene delivery system: Factors affecting the complexation

Stearic acid grafted chitosan oligosaccharide micelle as a promising vector for gene delivery system: Factors affecting the complexation
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硬脂酸接枝壳寡糖胶束作为基因传递系统的有前途的载体:影响络合的因素

DOI:
10.1016/j.ijpharm.2010.02.017
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发表时间:
2010-05-31
影响因子:
5.8
通讯作者:
Hu, Fu-Qiang
Hu, Fu-Qiang
中科院分区:
医学2区
文献类型:
--
作者:
Du, Yong-Zhong;Lu, Ping;Hu, Fu-Qiang

文献摘要

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通过壳寡糖(CSO)与硬脂酸(SA)的偶联反应,合成了不同分子量和硬脂酸接枝率的硬脂酸接枝壳寡糖(CSO-SA)。通过自组装形成阳离子聚合物胶束,并将其用于鱼类精子DNA的基因传递。考察了影响CSO-SA胶束与DNA络合及稳定性的因素。结果表明,随着CSO氨基取代度从9.79%增加到63.41%,CSO分子量为3 kDa时,其pKa值从8.16下降到6.02,而分子量对pKa值的影响较小。对于复合物的稳定性,溴化乙锭分析表明,氨基取代度低或分子量小的CSO与SA形成的复合物比氨基取代度高或分子量大的CSO形成的复合物更稳定。低pH和低离子强度的环境有利于配合物的稳定性。(C)2010 Elsevier B. V.保留所有权利。
Stearic acid (SA) grafted chitosan oligosaccharide (CSO-SA) with different molecular weight of chitosan oligosaccharide (CSO) and graft ratio of stearic acid were synthesized by coupling reaction of SA and CSO. The cationic polymeric micelles of CSO-SA via self-assemble formed and used for gene delivery of fish sperm DNA. Factors affecting complexation and stability of the complexes of CSO-SA micelles and DNA were investigated. The results indicated that pKa of CSO-SA with 3 kDa of CSO decreased from 8.16 to 6.02 as the substitution degree of amino groups of CSO in CSO-SA increased from 9.79% to 63.41%, whereas the molecular weight (M-W) of CSO less affected the pKa. As for the stability of complexes, ethidium bromide assay data demonstrated that the complexes consisting of CSO-SA with lower amino substitution degree or smaller molecular weight of CSO were more stable than that with the higher amino substitution degree or molecular weight of CSO. The results also presented that the low pH and ionic strength environment were in favor for the stability of complexes. (C) 2010 Elsevier B.V. All rights reserved.