硬脂酸接枝壳寡糖胶束作为一种有前途的基因传递系统载体：影响复合物形成的因素。

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

机构信息

College of Pharmaceutical Science, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, PR China.

出版信息

Int J Pharm. 2010 May 31;391(1-2):260-6. doi: 10.1016/j.ijpharm.2010.02.017. Epub 2010 Feb 17.

DOI:10.1016/j.ijpharm.2010.02.017

PMID:20170716

Abstract

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 3kDa 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.

摘要

通过 SA 与 CSO 的偶联反应，合成了不同分子量 CSO 和接枝率的 SA 接枝壳聚糖寡糖（CSO-SA）。CSO-SA 通过自组装形成阳离子聚合物胶束，用于鱼类精子 DNA 的基因传递。研究了影响 CSO-SA 胶束与 DNA 复合物的络合和稳定性的因素。结果表明，随着 CSO-SA 中 CSO 的氨基取代度从 9.79%增加到 63.41%，CSO-SA 的 pKa 从 8.16 降低到 6.02，而 CSO 的分子量（M（W））对 pKa 的影响较小。对于复合物的稳定性，溴化乙锭分析数据表明，氨基取代度较低或 CSO 分子量较小的 CSO-SA 组成的复合物比氨基取代度较高或 CSO 分子量较大的复合物更稳定。结果还表明，低 pH 值和离子强度环境有利于复合物的稳定性。