Preparation of anti-resistant stealthy liposomes by incorporating vincristine with quinacrine and the pharmacokinetics in Sprague-Dawley rats

Abstract

Abstract: Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups: each rat in the Group I was administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group II similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ± 7.1 nm and the encapsulation efficiencies of stealthy liposomes were > 90% for vincristine, and > 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0–24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0–24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.

Key words: Stealthy liposomal vincristine plus quinacrine, Stealthy liposomal vincristine plus quinacrine, HPLC, HPLC, Pharmacokinetics, Pharmacokinetics

CLC Number:

R943

Supporting:

Gong-Wen Liang, Wan-Liang Lu^*, Jin-Wei Wu, Ji-Hui Zhao, Ting Li, Yu-Teng Zhang, Hua Zhang, Jian-Cheng Wang, Xuan Zhang, Qiang Zhang. Preparation of anti-resistant stealthy liposomes by incorporating vincristine with quinacrine and the pharmacokinetics in Sprague-Dawley rats[J]. .

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