ABSTRACT
Objective To prepare hyaluronic acid-nricase liposomes (UHLP) and to investigate the activity and stability of UHLP and uricase (UC) in vitro. Methods UHLP was prepared using reverse-phase evaporation and observed by transmission electron microscopy. The entrapment efficiency, particle size and zeta potential of UHLP were detected. The physical and chemical properties of UC in free UC and UHLP-including the optimum pi I and temperature-thermal stability-storage stability, pi I stability, stability to trypsinase, and stability to metal ions and organic compounds, were examined. In addition, the mechanism by which UHLP promotes UC activity was also explored. Results The mean entrapment efficiency of UIILP was (57. 2 ± 3. 93)% (n = 3), mean particle size was (322. 6 ± 8. 2) nm (n=3), and mean zeta potential was (–19.4 ± 1.7) mV (n = 3). UHLP was round or oval in shape and was evenly distributed under transmission electron microscopy. The optimum temperature of UC in UHLP and free UC was 40°C -and the optimum pH values of UC in UHLP and free UC was 8. 0 and 8. 5, respectively. Thermal stability, storage stability, pi I stability, stability to trypsin and stability to metal ions and organic compounds of UC in UHLP were better than those in free UC. The envelopment of UC with UHLP increased the activity of UC by reversing conformation and exposing active center of UC. Conclusion UHLP can not only enhance the activity but also improve the stability of UC in vitro.
ABSTRACT
Objective To study the pharmacokinetics and bioequivalence of asparaginase (Asp) hyaluronic acid-graft-poly (ethylene glycol)/dimethyl-β-cyclodextrin (DCD) nanocapsules (AHDPs) in male Sprague-Dawley (SD) rats. Methods AHDPs were observed under the transmission electron microscope. The size, zeta potential and entrapment efficiency of AHDPs were examined. Asp activities were assayed after intravenous injection of AHDPs or free Asp in rats. Pharmacokinetic parameters were calculated by software DAS 2.1.1. Then the bioequivalence of AHDPs and free Asp were evaluated. Results The average particle size of AHDPs was (439.63±8.49) nm, zeta potential was (-20.43±2.20) mV, and entrapment efficiency was (55.75±4.11)% (n=3). AUC(0-48 h) of AHDPs and free Asp were (138.93±0.89) U•mL-1•h and (46.38±1.98) U•mL-1•h, the AUC0-∞ were (175.22±13.59) U•mL-1•h and (51.44±3.01) U•mL-1•h, and t1/2 was (4.46±1.04) h and (1.86±0.38) h, respectively. Compared with free Asp, the AUC0-48 h, AUC0-∞ and t1/2 of AHDPs were increased by 3.00, 3.40 and 2.40 times, respectively. The 90% confidential intervals of AUC0-48 h, AUC0-∞ and Cmax were 76.9%-78.3%, 76.9%-78.3% and 92.8%-94.4%, respectively. Conclusion AHDPs can prolong the biological half-life and improve the bioavailability of Asp in rats. AHDPs and free Asp are not bioequivalent.