title: [Pharmacokinetics and bioequivalence assessment of a self-assembled asparaginase nanocapsule in rats].
abstract: OBJECTIVE
  To study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-β-cyclodextrin nanocapsules (AHSP) in SD rats.
  
  
  METHODS
  The morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase.
  
  
  RESULTS
  AHSP had an average particle size of 413.80∓10.97 nm with a zeta potential of -20.37∓2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34∓1.82 U/mL and 46.38 ∓1.98 U/mL, and their AUC(0-∞) was 164.66∓6.88 U/mL and 51.44∓3.01 U/mL with half-lives of 4.62∓0.60 h and 1.86∓0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-∞), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-∞) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively.
  
  
  CONCLUSIONS
  AHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.E-mail: 396795576@qq.com.
authors.forename: Zijun
authors.initials: Z
authors.lastname: Yan
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Xie
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Hu
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001215:Asparaginase / Q000493:pharmacokinetics*; D001682:Biological Availability; D006207:Half-Life; D007275:Injections, Intravenous; D053769:Nanocapsules; D051381:Rats; D017207:Rats, Sprague-Dawley; D013810:Therapeutic Equivalency
chemical_list: D053769:Nanocapsules; D001215:Asparaginase