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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

  • 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。

     

    Abstract: 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 content (DLC),drug entrapment efficiency (DEE),particle size and Zeta potential were used to evaluate the effect of degree 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 anticancer drugs with improved drug loading content and stability.

     

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