Preparation and Oral Pharmacokinetics of Fenofibrate PEG2000-DSPE Micelles in Rats / 中国药师

ABSTRACT

Objective:To prepare fenofibrate PEG2000-DSPE micelles in order to improve the solubility of fenofibrate, and study the oral pharmacokinetics of the micelles in SD rats. Methods:Fenofibrate PEG2000-DSPE micelles were prepared and characterized. The rats were administrated with fenofibrate PEG2000-DSPE micelles and fenofibrate suspension, respectively. The blood samples were collected from eye socket and determined by HPLC. The compartmental pharmacokinetics was analyzed by DAS software. Results:Fenofibrate PEG2000-DSPE micelles were prepared successfully. The mean particle size was (23. 40 ± 3. 62) nm, the drug loading and the entrapment efficiency was (97. 65 ± 3. 32) % and (1. 33 ± 0. 32) %, respectively. The mean plasma concentration-time curves of fenofibric acid were both in accordance with two-compartment mode after oral administration of fenofibrate PEG2000-DSPE micelles and fenofibrate suspension in rats. After the oral administration, AUC(0-24) and Cmax of fenofibrate PEG2000-DSPE micelles was respectively 7-fold and 14-fold higher than that of fenofibrate suspension [(61. 41 ± 5. 71)μg·h·ml-1 vs (8. 49 ± 0. 66)μg·h·ml-1, and (9.67±1.65) μg·ml-1 vs (0.71 ±0.09) μg·ml-1]. The relative bioavailability of fenofibrate PEG2000-DSPE micelles was 723. 3%. Conclusion:The bioavailability and absorption rate of fenofibrate are both increased by the micelles remarkably when com-pared with those of fenofibrate suspension after oral administration. The PEG2000-DSPE micelles served as drug carrier for oral delivery present promising application perspectives.