化学组成对聚乙二醇化硬脂酰壳寡糖纳米胶束性能的影响  

Infl uence of Chemical Compositions on the Properties of PEGylated Stearyl Grafted Chitooligosaccharide Nanomicelles

作　　者：江东波[1] 张炜华[1] 刘建文[1] 沈熊[2] 翁伟宇[1] 

机构地区：[1]华东理工大学药学院,上海市新药设计重点实验室,上海200237 [2]复旦大学附属中山医院,上海200032

出　　处：《中国医药工业杂志》2014年第7期634-640,共7页Chinese Journal of Pharmaceuticals

基　　金：上海市科委基金(11DZ2260600)

摘　　要：合成了硬脂酰壳寡糖(COS-SA)和聚乙二醇化硬脂酰壳寡糖(PEG-COS-SA),两者在水中均可自组装成纳米胶束。考察了空白胶束和载盐酸多柔比星胶束的性质。结果表明,COS-SA中硬脂酸取代度主要影响临界胶束浓度,与硬脂酸/壳寡糖的投料比呈线性关系;载药胶束的粒径显著大于空白胶束;PEG修饰可进一步使胶束的粒径和临界胶束浓度增大、ζ电位减小。两种载药胶束的释药行为相似,均有明显的缓释作用。与COS-SA载药胶束相比,PEG化载药胶束对肿瘤细胞生长的抑制率较低,但血清稳定性良好,静脉注射后的长循环效果显著。提示化学组成对以壳寡糖衍生物为载体的纳米胶束性能有重要影响。Stearyl grafted chitooligosaccharide （COS-SA） and its PEGylated derivative （PEG-COS-SA）were synthesized.Both materials could self-assemble into nanomicelles in aqueous solution.The properties of the blank and doxorubicin hydrochloride nonamicelles with COS-SA or PEG-COS-SA as carrier were investigated.The results showed that there was a linear correlation between the substitution degree of stearic acid （SA） in COS-SA and the feed ratio of SA to COS.The substitution degree of SA affected the critical micelle concentration （CMC）.The particle size of the drug-loading nanomicelles was significantly larger than that of the corresponding blank nanomicelles.PEGylation could further increase the particle size and CMC but decrease the ζ potential.Both nanomicelles exhibited sustainedrelease profiles of doxorubicin and no significant differences in the release behavior were observed.Compared with the COS-SA nanomicelles,the PEG-COS-SA nanomicelles showed good serum stability,prolonged circulation time,but low cytotoxicity against tumor cells.It indicated that chemical composition was a decisive factor for the properties of nanomicelles with chitooligosaccharide derivatives as carriers.

关 键 词：硬脂酰壳寡糖 聚乙二醇化硬脂酰壳寡糖 胶束性质 细胞生长抑制 药动学 

分 类 号：R944.9[医药卫生—药剂学]