烷基化白蛋白的合成、表征以及对难溶性抗肿瘤药物的负载  

Synthesis,characterization and drug loading capacity of dodecyl serum albumin for insoluble antitumor drugs

作　　者：尹晓强[1] 霍美蓉[1] 周建平[1] 邹爱峰[1] 李静[1] 彭晓铃[1] 

机构地区：[1]中国药科大学药剂学教研室,南京210009

出　　处：《中国药科大学学报》2011年第4期319-323,共5页Journal of China Pharmaceutical University

基　　金：国家"重大新药创制"科技重大专项资助项目(No.2009ZX09310-004);教育部新教师基金资助项目(No.200803161017)~~

摘　　要：对牛血清白蛋白进行烷基化修饰,合成一系列两亲性的十二烷基白蛋白(DSA)衍生物,并采用1H NMR、元素分析以及热重分析法对其进行结构确证;以芘作为荧光探针,测定了它们的临界胶束浓度;采用透析法制备一系列紫杉醇烷基白蛋白(PTX-DSA)纳米胶束,以载药量、包封率、粒径和Zeta电位作为评价指标,研究了取代度对紫杉醇载药能力的影响,然后采用透射电子显微镜(TEM)和广角X线衍射(WAXD)技术分别对载药胶束进行了表征。研究结果表明,取代度在7.72%～31.71%之间的DSA能在水溶液中自组装形成纳米胶束,其紫杉醇的载药量和包封率分别高达(32.14±4.13)%和(87.25±16.18)%,而其粒径和Zeta电位分别为(135.83±2.47)nm和-(31.07±0.51)mV;TEM显示该聚合胶束呈现出球形或类球形结构;WAXD研究结果表明,紫杉醇均匀分散在聚合物胶束中。DSA可作为难溶性抗肿瘤药物的载体,具有载药量高、稳定性好等优点。Based on reductive amination,dodecyl serum albumin（DSA） was synthesized and confirmed by 1H NMR,elemental analysis and TG analysis.The CMC values of DSA were determined by fluorescence chromatography using pyrine as a probe.Paclitaxel（PTX） DSA micelles were prepared by dialysis and characterized by transmission electron microscope（TEM） and wide angle X-ray diffraction（WAXD）.Then a series of indicators,including drug loading con-tent（DLC）,drug entrapment efficiency（DEE）,particle size and Zeta potential were used to evaluate the effect of de-gree of substitution（DS） of alkyl segments of DSA on the drug loading capacity of PTX was investigated.The results indicated that DSA with a degree of substitution（DS） in the range of 7.72% to 31.71% was successfully synthesized and could self-assemble into micelles in water.PTX-DSA micelles exhibited excellent drug loading capacities for PTX with DLC and DEE high to（32.14 ± 4.13） % and（87.25 ±16.18） %,respectively,at the same time,the particle size and Zeta potential were（135.83 ±2.47） nm and-（31.07 ±0.51） mV,respectively.A spherical shape and a uniform size distribution were proved by TEM.WAXD of PTX-DSA micelles indicated that PTX was transferred to amorphous state after loading.It was concluded that the present DSA could be a potentially drug delivery system for insoluble anti-cancer drugs with improved drug loading content and stability.

关 键 词：烷基化白蛋白 紫杉醇 胶束 增溶 理化性质 

分 类 号：R944[医药卫生—药剂学]