Pharmacokinetics of hyaluronic acid-graft-poly(ethylene glycol)/α-cyclodextrin nanocapsules loaded with asparaginase / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the pharmacokinetics and bioequivalence of hyaluronic acid-graft-poly(ethylene glycol)/α-cyclodextrin nanocapsules loaded with asparaginase (AHAPs) in SD rats. METHODS: Rats were randomly divided into two groups. After intravenous injecting AHAPs and free AN, the activity of AN in two groups was assayed at different time points. The pharmacokinetic parameters were calculated by software DAS2.1.1 and the bioequivalence of free AN and AHAPs was judged. RESULTS: AUC0-48 h of AHAPs and free AN were (132.26±1.59) and (46.38±1.98) U·h·mL-1. MRT0-48 h, of AHAPs and free AN were (3.64±0.04) and (1.76±5.99) h. The tmax of AHAPs and free AN were (0.75±0) and (0.08±0) h, respectively. The results showed that AUC0-48 h, MRT0-48 h and tmax of AHAPs increased to 2.85, 2.07 and 9.37 times, respectively, as compared with free AN. The 90% confidential intervals of AUC0-48 h, AUC0-∞ and ρmax of tested formulation were 77.0%-78.5%, 77.0%-78.5%, 94.4%-96.0%, respectively. The tmax checked by nonparametric method has significant difference (P<0.05) between AHAPs and free AN. CONCLUSION: AHAPs can improve the bioavailability and extend the action time of AN in rats. AHAPs and free AN were not bioequivalent. And AHAPs had better pharmacokinetics properties in rats.