光敏型壳寡糖聚合物胶束的制备及其光响应性质考察  

Preparation and Photo-activity of Photo-responsive Polymer Micelles Based on Chitosan Oligosaccharide

作　　者：张叶叶 卢光照 邹豪 ZHANG Yeye;LU Guangzhao;ZOU Hao(Dept.of Pharmacy,Zhongshan Hospital,Fudan University,Shanghai 200032;Dept.of Pharmaceutics,School of Pharmacy,Navy Medical University(Second Military Medical University),Shanghai 200433)

机构地区：[1]复旦大学附属中山医院药剂科,上海200032 [2]海军军医大学(第二军医大学)药学院药剂学教研室,上海200433

出　　处：《中国医药工业杂志》2020年第10期1288-1295,共8页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金项目(30801441和81773278);军队后勤科研重大项目(AWS14J011)。

摘　　要：采用化学合成法将连接光敏基团的十二烷基长链疏水段NMDB-ester连接至壳寡糖(COS)链上,合成了4种接枝率(40.3%、49.8%、58.1%、64.5%)的光敏型聚合物材料COS-NMDB。并且,基于该材料以透析法制备了载尼罗红(COS-NMDB-NR)胶束,初步筛选了制备胶束的最佳溶剂及最适疏水段接枝率,同时研究了该胶束的光响应释药性质。结果表明,制备胶束的最佳溶剂为N,N-二甲基甲酰胺(DMF)、最佳接枝率为49.8%(即合成产物COS-NMDB7.5)。所得胶束稳定性良好,其粒径、多分散系数和ζ电位分别为(55.0±2.3)nm、0.199±0.024和(29.0±1.3)mV。相比文献报道的光敏型壳寡糖材料COS-NB,COS-NMDB显示出更好的载药性能。紫外光响应性测试表明COS-NMDB胶束具有光响应释药行为;光照后,胶束解组装,其球状粒子形态坍塌,并释放出模型药物,可以作为光敏型药物载体进一步研究。The photo-responsive chitosan oligosaccharide(COS)was structurally modified with NMDBester that contained photo-trigger to obtain a new photo-responsive amphiphilic block copolymer,COS-NMDB,with different grafting ratios of 40.3%,49.8%,58.1%and 64.5%.Then,the nile red(NR)-loaded photo-responsive micelles based on COS-NMDB with different grafting ratios were prepared,respectively.The influences of organic solvent and grafting ratio of COS-NMDB on the properties of the micelles were investigated to select the optimal parameters.At the same time,photo-responsive release properties of the micelles were studied preliminarily.The results showed that N,N-dimethylformamide(DMF)was the suitable solvent and the optimal grafting ratio was selected as 49.8%(COSNMDB7.5)for preparing micelles.The particle size,polydispersity index andζpotential of the optimal micelles based on COS-NMDB7.5 were(55.0±2.3)nm,0.199±0.024 and(29.0±1.3)mV,respectively.And the optimal micelles also showed higher stability.Compared with COS-NB reported in literature,COS-NMDB with long dodecyl chain showed better drug loading performance.After UV irradiation,the COS-NMDB micelles were disassembled and the spherical particles were collapsed.NR could be released in a light controlled manner,which was induced by gradual photo-cleaving.It was concluded that the photo-responsive COS-NMDB could be used as a light-sensitive drug carrier for further research.

关 键 词：壳寡糖 胶束 光敏型聚合物 制备 载药性能 光响应释药 

分 类 号：R944.9[医药卫生—药剂学]