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.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2014年第7期634-640,共7页
Chinese Journal of Pharmaceuticals
基金
上海市科委基金(11DZ2260600)
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
stearyl grafted chitooligosaccharide
PEGylated stearyl grafted chitooligosaccharide
micelle property
cell growth inhibition
pharmacokinetics
