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
Aim To investigate the stabilities and related mechanism of sulfobutyl ether-β-cyclodextrin liposomes loaded with asparaginase(ASDL).Methods Reverse evaporating method was used for the preparation of ASDL,and the acid-base stability,thermal stability,antitrypsin stability,plasma stability and storage stability of ASDL were tested.Moreover,fluorescence spectrum method was utilized to explore the stability enhancement mechanisms of ASDL.Results The results of stability showed that the acid-base stability,thermal stability,antitrypsin stability,plasma stability and storage stability of ASDL were all superior to asparaginase.Fluorescence experiment results indicated that the improved characteristics of ASDL might be related to the changes of the surrounding microenvironment of fluorescent chromophore or the structure of hydrophobic.Conclusion ASDL can effectively protect asparaginase from the external environment,such as hydrolase,pH,temperature and so on,to improve the stabilities of asparaginase.