Preparation and evaluation of docetaxel-loaded albumin nanoparticles for intravenous administration

多烯紫杉醇结合白蛋白纳米粒的制备及体内外评价(英文)

Docetaxel （DTX） was incorporated into albumin nanoparticles to form the docetaxel loaded nanoparticles （DTX-NPs） with a high-pressure homogenization method. The purpose of this procedure was to improve the solubility, stability and biocompatibility of DTX. In our study, particle size, zeta potential, size distribution, and encapsulation efficiency were investigated. The crystalloid state of DTX in nanoparticles was further determined by the X-ray diffraction technique. The hemolysis rate, pharmacokinetics and pharmacodynamics of the DTX-NPs were analyzed and compared with the injectable docetaxel solution （DTX-Sol）, which was fabricated according to the formulation of the commercial Taxotere. It demonstrated that the DTX-NPs were prepared successfully with these properties, including the （193±4） nm size, （-30±1） mV zeta potential and 69%±2% encapsulation efficiency. Higher stability was achieved in the lyophilized nanoparticles compared to that in the nanoparticle suspension. Furthermore, less hemolysis effect was observed in the DTX-NPs than that in the DTX-Sol. The pharmacokinetic and pharmacodynamic behaviors of the DTX-NPs were similar as that of DTX-Sol based on the in vivo experiments. In conclusion, albumin nanoparticles may act as a useful and safe carder for DTX.

本文采用了高压乳匀法制备载多烯紫杉醇白蛋白纳米粒,以期改善目前临床上多烯紫杉醇注射液的不良反应。考察了多烯紫杉醇白蛋白纳米粒的粒径、电位、包封率,并采用X射线衍射技术对多烯紫杉醇在纳米粒中的存在形式进行考察,还评价了多烯紫杉醇纳米粒的溶血性,药动学和药效学行为,以市售静注用多烯紫杉醇溶液(泰素帝)作为参比制剂。研究结果表明,多烯紫杉醇白蛋白纳米粒粒径(193±4)nm,电位(-30±1)mV和包封率为69%±2%,纳米粒冻干后具有良好的稳定性。与多烯紫杉醇溶液相比,白蛋白纳米粒制剂的溶血性有非常显著的改善(P<0.01),而药动学和抗肿瘤药效学方面两者较为相似。由此可见,白蛋白纳米粒将可作多西紫杉醇药物体内静脉注射用的安全有效载体。