卡铂长循环脂质体的制备及其在大鼠体内的药动学

Preparation and Pharmacokinetics in Rats of Carboplatin Long-circulating Liposomes

该研究采用被动载药的方式制备了分别含卡铂20和10 mg/ml的卡铂长循环脂质体A、B,对其理化性质进行了分析,并应用原子吸收光谱法测定血浆中的药物浓度以评价其在SD大鼠体内的药动学行为。研究结果表明,制得的卡铂脂质体分散性、流动性、重现性良好,粒径约为100 nm。卡铂长循环脂质体A、B的AUC分别为(1667.87±642.98)和(1359.43±583.61)h·mg·L^(-1),c_(max)分别为(96.72±27.21)和(63.04±22.15)mg/L,t_(1/2)分别为(15.02±5.72)和(22.90±5.64)h,在同等给药剂量下与游离药物组相比,均显著提高。卡铂长循环脂质体可延长药物在血液中的循环时间,有利于提高药物在肿瘤组织中的浓度,进而增强疗效,有望为卡铂新剂型的研究提供思路和参考。

In this study,carboplatin long-circulating liposomes A(20 mg/ml)and B(10 mg/ml)were prepared by passive drug loading,and their physicochemical properties were analyzed.The plasma drug concentration was determined by atomic absorption spectrometry to evaluate the pharmacokinetics in rats.The results showed that the prepared carboplatin liposomes had good dispersibility,fluidity and reproducibility,and the particle size was about 100 nm.The AUC of carboplatin long-circulating liposomes A and B were(1667.87±642.98)and(1359.43±583.61)h·mg·L^(-1),respectively,and the c_(max) were(96.72±27.21)and(63.04±22.15)mg/L,respectively,t_(1/2) were(15.02±5.72)and(22.90±5.64)h,which were significantly increased compared with the free drug group at the same dose.Carboplatin long-circulating liposomes can prolong the circulation time of the drug in the blood,which is beneficial to increase the drug concentration in the tumor tissue,thereby enhancing the curative effect.This study provided ideas and references for researching new carboplatin dosage forms.