Study on preparation and in vivo pharmacokinetics in rats of morellic acid B mPEG liposome / 中草药

ABSTRACT

Objective: To optimize the preparation process of morellic acid B (MAB) mPEG liposomes (MAB-mPEG-LPS), and to study the in vitro release behavior and pharmacokinetics of MAB-mPEG-LPS in rats. Methods: The analytical method of MAB was established; Encapsulation efficiency and particle size were used as the indexes to optimize the mPEG liposomes by orthogonal test, and the highest encapsulation efficiency of MAB-mPEG-LPS was obtained; Transmission electron microscope was used to observe the surface morphology of MAB-mPEG-LPS, and the stability of MAB-mPEG-LPS was measured in 60 d. Dialysis method was also adopted to study the MAB-mPEG-LPS release in vitro; Male SD rats were injected with MAB (1.50 mg/kg), MAB-LPS (1.50 mg/kg), MAB-mPEG-LPS (1.50 mg/kg) via tail vein, and differences in pharmacokinetics parameters of MAB, MAB-LPS, and MAB- mPEG-LPS were compared. Results: The optimized formula of MAB-mPEG-LPS HSPC was 128 mg, mPEG was 10 mg, HSPC-CHOL was 8∶1. Encapsulation efficiency of MAB-mPEG-LPS was 83.21%. MAB-mPEG-LPS had uniform particle size and smooth surface; In vitro release results showed that the MAB-mPEG-LPS had slow release and long-term effect. It was stable in 60 d; In vivo study showed that t1/2β of MAB in MAB-mPEG-LPS was 66.925 min, which was 4.43 fold to MAB. MAB-mPEG-LPS was 3.29 fold to MA-LPS; AUC0-∞ of MAB in MAB-mPEG-LPS was 241.372 mg∙min/L, which was 3.64 fold to MAB. MAB-mPEG-LPS was 1.99 fold to MAB-LPS. Conclusion: MAB-mPEG-LPS could prolong the circulation time and increase AUC0-∞ of MAB in rats.