ABSTRACT
Objective To investigate the physicochemical properties and pharmacokinetics of L-asparaginase loaded hydroxypropyl-β-cyclodextrin liposome (AHL) in rats. Methods AHL was prepared by reverse evaporation method, and the entrapment rate, particle size, zeta potential and morphology of AHL were observed. Twelve SD rats were randomly divided into two groups. One group was injected with AHL, and the other group was injected with L-asparaginase (L-ASN). The blood samples were taken from infraorbital venous plexus, and the activity of L-ASN in the samples were determined and the activity-time curve was plotted. Main pharmacokinetic parameters were calculated by software DAS2.1.1. Results The average entrapment efficiency of AHL was (53.53±0.58)%, with an average particle size of (388.99±2.02) nm and an average zeta potential of (－8.56±0.75) mV. The pharmacokinetic parameters for AHL and L-ASN were: 0-48 h area under curve (198.79±9.15) U/(mL • h), (57.78±2.90) U/(mL • h); 0-48 h mean resident time (4.61±0.09) h, (2.09±0.05) h; peak concentration (32.32±1.33) U/mL, (26.82±1.38) U/mL; and time to peak (1.08±0.20) h, (0.10±0.04) h, respectively. The relative bioavailability of AHL was 344.05%. Conclusion AHL can improve the pharmacokinetics and enhance the bioavailability of L-ASN.
ABSTRACT
OBJECTIVE: To investigate the stability and pharmacokinetics of chitosan-modified L-asparaginase liposomes. METHODS: The activities of L-asparaginase and chitosan-modified L-asparaginase liposomes in blank rat plasma were determined at different time. L-asparaginase and chitosan-modified L-asparaginase liposomes were intravenously injected to rats through tail vein. The pharmacokinetic parameters were calculated by DAS. RESULTS: The activity of chitosan-modified L-asparaginase liposomes in plasma was significantly higher than that of L-asparaginase. The AUC0-48 h of chitosan-modified L-asparaginase liposomes was as 3.3 times as that of L-asparaginase. And the MRT0-48 h of chitosan-modified L-asparaginase liposomes was as 2.3 times as that of L-asparaginase. CONCLUSION: Chitosan-modified L-asparaginase liposomes can improve the stability and bioavailability of L-asparaginase.