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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PCLPEG-PCL胶束的体内药代动力学,并用DAS 2.0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93 nm,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(t1/2β)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。
OBJECTIVE To prepare a novel injectable paclitaxel-polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles and to evaluate and compare its pharmacokinetics with commercial paclitaxel injection in rats Kinetic properties. Methods Paclitaxel-loaded PCL-PEG-PCL micelles were prepared by membrane-hydration-ultrasonication using PCL-PEG-PCL as carrier material. The pharmacokinetics of paclitaxel-loaded PCLPEG-PCL micelles were observed by tail vein injection of paclitaxel injection in the market of SD rats. The relevant parameters were calculated by DAS 2.0 pharmacokinetic data software. Results The paclitaxel-loaded PCL-PEG-PCL micelles showed a spherical shape with a clear core-shell structure. The average particle diameter was 93 nm, the polydispersity index was 0.19, the drug loading was 28.98% and the entrapment efficiency was 94.36% . In vitro release study showed that paclitaxel PCL-PEG-PCL micelles with sustained release effect. Pharmacokinetic studies showed that the two formulations were in line with two-compartment model, the elimination half-life (t1 / 2β) of commercial paclitaxel injection and paclitaxel polymer micelles were (1.96 ± 0.27) h and (12.65 ± 1.77) The mean time to stay (MRT) was (0.93 ± 0.19) h and (11.18 ± 1.41) h, respectively. The total body clearance (CL) were (0.44 ± 0.05) L · kg / h and (0.10 ± 0.01) L · kg / h, the area under the drug-time curve (AUC0-∞) was (17.15 ± 2.35) mg · h / L and (73.82 ± 10.38) mg · h / L, respectively. Conclusions A novel injectable paclitaxel-loaded PCL-PEG-PCL micelles was successfully prepared. The pharmacokinetics study showed that paclitaxel loaded PCL-PEG-PCL micelles could prolong the circulating time of paclitaxel in blood and eliminate the half- Significantly improve the bioavailability, is a potential paclitaxel slow controlled release of new dosage forms.