脑靶向多柔比星胶束的制备及体外性质研究

发布时间：2018-11-17 09:39

【摘要】：目的:制备脑靶向多柔比星胶束,并评价其体外理化性质。方法:合成葡萄糖修饰的泊洛沙姆P105衍生物(葡萄糖-泊洛沙姆P105),考察其氢核磁共振(1H-NMR)图谱,计算葡萄糖的偶联率。用透析法以葡萄糖-泊洛沙姆P105制备脑靶向多柔比星胶束,用单因素法考察处方中多柔比星的投药量、二甲基亚砜(DMSO)与水相的比例对胶束包封率和载药量的影响;考察所制胶束的粒径、Zeta电位、形貌、体外释药情况;以星型胶质细胞和小鼠脑微血管内皮(BMVECs)细胞模拟体外血脑屏障(BBB),比较多柔比星水溶液、多柔比星普通胶束、多柔比星胶束透过BBB的转运率。结果:合成的葡萄糖-泊洛沙姆P105的葡萄糖偶联率为88.7%。随着多柔比星投药量和DMSO有机相比例的增加,包封率和载药量均呈先升高后降低的趋势,其中多柔比星为7 mg、DMSO与水相的体积比为0.10∶1时包封率和载药量最好;所制胶束的平均粒径为(26.7±5.4)nm,Zeta电位为(-6.48±0.64)m V,透射电镜照片显示呈球状;体外释药动力学符合Weibull方程;多柔比星胶束的BBB转运率明显高于多柔比星普通胶束。结论:成功制得具有脑靶向功能的多柔比星胶束。
[Abstract]:Aim: to prepare brain-targeted doxorubicin micelles and evaluate their physical and chemical properties in vitro. Methods: glucose-modified Poloxamer P105 derivatives (glucose-Poloxamer P105) were synthesized, and their hydrogen NMR (1H-NMR) spectra were investigated, and the coupling rate of glucose was calculated. The brain targeted doxorubicin micelles were prepared from glucose Poloxamer P105 by dialysis method. The dosages of doxorubicin and the ratio of dimethyl sulfoxide (DMSO) to water phase on the micelle encapsulation efficiency and drug loading were investigated by single factor method. The particle size, Zeta potential, morphology and drug release in vitro of the micelles were investigated. The transport rate of doxorubicin in aqueous solution, ordinary micelle of doxorubicin and micelle of doxorubicin through BBB was simulated by astrocytes and (BMVECs) cells of mouse brain microvascular endothelial cells in vitro. Results: the glucose coupling rate of glucose-Poloxamer P105 was 88. 7%. With the increase of doxorubicin dosage and DMSO organic phase ratio, the entrapment efficiency and drug loading amount increased first and then decreased, in which the volume ratio of doxorubicin 7 mg,DMSO to water was 0.10: 1, the entrapment efficiency and drug loading capacity were the best. The average particle size of the micelles was (26.7 卤5.4) nm,Zeta potential (-6.48 卤0.64) m V,), and the in vitro release kinetics was in accordance with the Weibull equation. The BBB transport rate of doxorubicin micelles was significantly higher than that of ordinary micelles. Conclusion: doxorubicin micelles with brain targeting function were successfully prepared.
【作者单位】：黄山学院化学化工学院制药工程系;黄河科技学院;
【基金】：安徽省自然科学基金项目(No.1308085QH139)
【分类号】：R943;R96

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