Lim Chang-Baek, Abuzar Sharif Md, Karn Pankaj Ranjan, Cho Wonkyung, Park Hee Jun, Cho Cheong-Weon, Hwang Sung-Joo
College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
College of Pharmacy, Yonsei University, Incheon 21983, Korea.
Pharmaceutics. 2019 Nov 8;11(11):589. doi: 10.3390/pharmaceutics11110589.
Here, we aimed to prepare and optimize liposomal amphotericin B (AmB) while using the supercritical fluid of carbon dioxide (SCF-CO) method and investigate the characteristics and pharmacokinetics of the SCF-CO-processed liposomal AmB. Liposomes containing phospholipids, ascorbic acid (vit C), and cholesterol were prepared by the SCF-CO method at an optimized pressure and temperature; conventional liposomes were also prepared using the thin film hydration method and then compared with the SCF-CO-processed-liposomes. The optimized formulation was evaluated by in vitro hemolysis tests on rat erythrocytes and in vivo pharmacokinetics after intravenous administration to Sprague-Dawley rats and compared with a marketed AmB micellar formulation, Fungizone, and a liposomal formulation, AmBisome. The results of the characterization studies demonstrated that the SCF-CO-processed-liposomes were spherical particles with an average particle size of 137 nm (after homogenization) and drug encapsulation efficiency (EE) was about 90%. After freeze-drying, mean particle size, EE, and zeta potential were not significantly changed. The stability study of the liposomes showed that liposomal AmB that was prepared by the SCF method was stable over time. In vivo pharmacokinetics revealed that the SCF-CO-processed-liposomes were bioequivalent to AmBisome; the hemolytic test depicted less hematotoxicity than Fungizone. Therefore, this method could serve as a potential alternative for preparing liposomal AmB for industrial applications.
在此，我们旨在采用二氧化碳超临界流体（SCF-CO₂）法制备并优化两性霉素B脂质体（AmB），并研究经SCF-CO₂处理的脂质体两性霉素B的特性和药代动力学。在优化的压力和温度条件下，通过SCF-CO₂法制备含有磷脂、抗坏血酸（维生素C）和胆固醇的脂质体；还采用薄膜水化法制备常规脂质体，然后与经SCF-CO₂处理的脂质体进行比较。通过对大鼠红细胞进行体外溶血试验以及对Sprague-Dawley大鼠静脉给药后的体内药代动力学对优化后的制剂进行评估，并与市售的两性霉素B胶束制剂Fungizone和脂质体制剂AmBisome进行比较。表征研究结果表明，经SCF-CO₂处理的脂质体为球形颗粒，平均粒径为137 nm（均质后），药物包封率（EE）约为90%。冻干后，平均粒径、EE和zeta电位无显著变化。脂质体的稳定性研究表明，通过SCF法制备的脂质体两性霉素B随时间推移具有稳定性。体内药代动力学研究表明，经SCF-CO₂处理过的脂质体与AmBisome具有生物等效性；溶血试验显示其血液毒性低于Fungizone。因此，该方法可作为工业应用中制备脂质体两性霉素B的一种潜在替代方法。
