载紫杉醇聚己内酯-聚乙二醇-聚己内酯胶束的制备及药代动力学研究简

目的制备新型可注射用载紫杉醇聚己内酯-聚乙二醇-聚己内酯（PCl-PEG-PCL）胶束，并评价和比较其与市售紫杉醇注射液在大鼠体内的药代动力学性质。方法以PCL-PEG-PCL为载体材料，通过薄膜-水化-超声法制备出载紫杉醇PCl-PEG-PCL胶束，并对其进行表征。以市售紫杉醇注射液为对照．采用SD大鼠尾静脉注射后观察载紫杉醇PCL-PEG-PCL胶束的体内药代动力学．并用DAS2．0药代动力学数据软件计算相关参数。结果载紫杉醇PCL-PEG-PCL胶束呈大小均匀的球形，具有明显的核壳结构；平均粒径为93nm，多分散系数为0．19；载药量为28．98％，药物包封率为94．36％。体外释放研究表明．载紫杉醇PCL-PEG-PCL胶束具有缓释效果。药代动力学研究表明．两种制剂均符合二房室模型．市售紫杉醇注射液和紫杉醇聚合物胶束消除半衰期（t1/2）分别为（1．96±0．27）h和（12．65±1．77）h，平均滞留时间（MRT）分别为（0．93±0．19）h和（11．18±1．41）h，体内总清除率（CL）分别为（0．44±0．05）L·kg／h和（0．10±0．01）L·kg／h，药-时曲线下面积（AUC0-∞）分别为（17．15±2．35）mg·h／L和（73．82±10．38）mg．h／L。结论成功制备了新型可注射用载紫杉醇PCL-PEG-PCL胶束．药代动力学研究表明．所研制的载紫杉醇PCL-PEG-PCL胶束明显延长紫杉醇在血液中的循环时间及消除半衰期．显著提高生物利用度，是一种有潜力的紫杉醇缓控释新剂型。

Preparation and pharmacokinetic study of paclitaxel-loaded PCL-PEG-PCL polymeric micelles

Objective To develop novel paclitaxel-loaded polymeric micelles（PPM） for intravenous injection, and evaluate and compare the pharmacokinetics of PPM and conventional paclitaxel injection（Taxol ） in rats. Methods The PPM were prepared from PCL-PEG-PCL copolymers using thin film-hydration-sonication method, and its properties were then characterized. PPM and Taxol were intravenously injected to rats to study their pharmacokinetics, and the pharmaeokinetic parameters were obtained using the DAS 2.0 program. Results The PPM exhibited homogeneous spherical shapes with apparent core-shell morphology. The average diameter was 93 nm with polydispersity index of 0.19. The drug-loading content and the encapsulation efficiency was 28.98 % and 94.36 %, respectively. In vitro release study indicated that paclitaxel was released in a controlled and sustained fashion. The plasma paclitaxel concentration-time profiles after dosing of both Taxol ~ and PPM were best fitted to two- compartment model. The main pharmacokinetic parameters of Taxol and PPM were as follows： the plasma elimination half-life were （1.96 ± 0.27） hours and （12.65 ± 1.77） hours; the mean residence time0VIRT） were （0.93 ± 0.19） hours and （11.18± 1.41） hours; the plasma clearance rates（CL） were （0.44 ±0.05） L.kg/h and （0.10 ± 0.01） L .kg/h; the areas under the plasma concentration-time eurve（AUC0-∞） were （17.15 ± 2.35） mg.h/L and （73.82 ± 10.38） mg.h/L, respectively. Conclusion It is demonstrated that the novel PPM for intravenous injection are successfully developed. Pharmacokinetic results indicated that the PPM has longer systemic circulation time, slower plasma elimination rate and higher bioavailability than those of Taxol . The prepared polymeric micelles might be a potential drug delivery system for paclitaxel delivery.