Preparation and pharmacokinetics of gambogic acid long-circulating liposomes / 中草药

ABSTRACT

Objective: To optimize the preparation process of gambogic acid (GA) liposomes and study the in vitro and in vivo release. Methods: The detection method of GA was established, using the Box-Behnken experiment design to optimize liposomes formula, GA liposomes were obtained with the highest encapsulation efficiency; Using scanning electron micrographs (SEM) to observe liposome surface morphology, using the dialysis method to study the liposome release in vitro, we also measured the stability of liposome in 15 d; Male Wistar rats were injected with GA or GA liposomes (1 mg/mL) via tail vein, UPLC-MS/MS method was used to determine the drug concentration, and differences in pharmacokinetic parameters of the two drugs were compared. Results: After Box-Behnken optimization, the encapsulation efficiency of liposomes was 92.3%, and the optimized liposomes formula is cholesterol of 440 mg, egg phosphatidylcholine of 1823 mg,,and istearoyl phosphoethanolamine-PEG 2000 of 705 mg, liposomes had uniform particle size and smooth surface; In vitro release results showed that the liposomes could be gentle and slowly release and had a long- term effect. The liposomes were stable keeping in 4 ℃ within 15 d; In in vivo study, the half-life of GA liposome was 9.97 h, 4.43 times of GA; AUC0-24 h of GA liposome was 22.55 μg∙h/mL, 4.73 times of GA. Conclusion: Compared with GA, GA liposome has the characteristics of long-circulating, high blood drug concentration, and could release smoothly.