多西紫杉醇白蛋白纳米粒的制备及体外评价

目的：制备多西紫杉醇白蛋白纳米粒，考察白蛋白和多西紫杉醇的处方量及乙醇加入量等因素对其形态、粒径、Zeta电位、收率、包封率、载药量和体外释药特性的影响，并对处方工艺进行优化。方法：采用去溶剂化-化学交联法制备多西紫杉醇白蛋白纳米粒，透射电镜观察纳米粒形态，马尔文激光粒度仪测定其粒径分布及Zeta电位，考马斯亮兰-酶标仪法测定纳米粒收率，HPLC法测定纳米粒包封率和载药量；以累积释药百分率为指标，通过方程拟合释药曲线，考察制剂的体外释药特性。处方优化采用星点设计-效应面优化法，应用SAS统计软件对数据进行处理。结果：优化处方制得的纳米粒为类球形，平均粒径65．3nm，Zeta电位-31．4mV，纳米粒收率95．0％，包封率74．3％，载药量4．65％，制剂24小时体外累积释药百分率为74．4％。结论：难溶性抗癌药物多西紫杉醇可以采用去溶剂化-化学交联法制备成白蛋白纳米粒，其粒径小，稳定性高，可显著提高多西紫杉醇在水相中的浓度。其优化处方中药物的释放显著慢于原料药磷酸盐缓冲溶液的释放，具有缓释效果。

Preparation and In Vitro Evaluation of Bovine Serum Albumin Nanoparticles Containing Docetaxel

Objective： To prepare and evaluate in vitro bovine serum albumin nanoparticles containing docetaxel （DT-BSA-NPs） and to optimize the formulation thereof. Methods： DT-BSA-NPs were prepared by desolvation-chemical crosslinking method. The morphology of the NPs was observed by TEM. The distribution of particle size and Zeta potential of the NPs were determined by Malveru particle size analyzer. The yield of the NPs was quantified by Bradford protein assay method. The encapsulation efficiency and drug-loading content of the NPs were examined by HPLC method. The property of their release in vitro was investigated, based on the measure of accumulated release ratio and the fitting of release curve. Their formulation was optimized by Central composite design-Response surface methodology and the data were processed using SAS statistical software. Results： The optimized result showed that DT-BSA-NPs were spherical with an average diameter of 65.3 nm, Zeta potential of - 31.4 mV, yield of 95.0%, drug-loading content of 4.65%, encapsulation efficiency of 74.3% and 24 h-accumulated release ratio of 74.4%. Conclusion： This formulation method could significantly increase the concentration of DT in water. DT- BSA-NPs prepared by this method exhibited a small particle size, high stability and sustained release in vitro.