Preparation and pharmacokinetic study of asiatic acid loaded chitosan-deoxycholic acid polymeric micelles in rats / 中草药

ABSTRACT

Objective To prepare asiatic acid (AA) loaded chitosan-deoxycholic acid self-assembled micelles (AA-CS-DCA PMs) adopting chitosan-deoxycholic acid (CS-DCA) as carriers and investigate its pharmacokinetic characteristics in rats. Methods AA-CS-DCA PMs were prepared by ultrasonic dispersion method. The characteristics of micelles were evaluated by the distribution of particle size, Zeta potential, drug loading, encapsulation efficiency, and in vitro release. Model of bile drainage was established in conscious rats and pre-column derivatization HPLC method was used to determine the concentration of AA in bile. Moreover, the pharmacokinetics characteristics of AA-CS-DCA PMs in vivo was evaluated by tmax, Cmax and AUC0-t. Results The particle size was (70.5 ± 9.8) nm, the Zeta potential was (38.4 ± 0.8) mV, and encapsulation efficiency and drug loading were (77.8 ± 1.2)% and (11.7 ± 0.2)%, respectively. The in vitro release profile showed a sustained release property. In vivo study showed that Cmax of AA-CS-DCA group (26.05 ± 3.04) μg/h was 2.8 times higher than that of the control group (9.19 ± 1.12) μg/h; The tmax of AA-CS-DCA PMs group prolonged significantly (P < 0.05) in biliary excretion (2 h vs 1 h) and the elimination half-life t1/2 was 1.8 times of the control group [(2.68 ± 1.71) h vs (1.49 ± 0.38 h)]. In addition, the AUC0-24 h which reflected the degree of drug absorption increased by 200% compared with the control group [(99.05 ± 12.83) μg vs (33.56 ± 8.33) μg]. Conclusion The chitosan- deoxycholic acid self-assembled micelles can raise the concentration of AA and prolong the retention time in vivo, which effectively improve the oral bioavailability of AA.