两性霉素B及其卵磷脂-胆固醇脂质体降解动力学研究

Studies on degradation kinetics of amphotericin B in solution and liposome composed by egg phospholipid and cholesterol

目的考察以卵磷脂、胆固醇为膜材制备的两性霉素B脂质体的稳定性及降解动力学。方法应用高效液相色谱法考察光和热对两性霉素B溶液及其脂质体中药物稳定性及降解动力学的影响,并拟合其降解动力学模型,求算降解半衰期。结果两性霉素B溶液及其脂质体光降解分别符合一级和零级动力学过程,降解半衰期分别为2.6和24.7d;热降解过程分别符合零级动力学和Higuchi方程;40℃下半衰期分别为27.8和1532.8d;60℃下半衰期分别为8.2和17.9d。结论脂质体可明显降低两性霉素B的光和热降解,延长药物降解半衰期,显著提高两性霉素B的稳定性。

Objective To study the stability and degradation kinetics of amphotericin B in liposome. Methods The light and thermal stabilities of amphotericin B in liposome and solution were determined by detecting its content using HPLC and the degradation kinetics was also investigated. Results The light degradation kinetics of amphotericin B in liposome and solution fit the zero- and first-order equations, and their half lives were 24.7d and 2.7d, respectively. While their thermal degradation kinetics complied with the Higuchi model and zero-order equations, respectively. The amphotericin B in liposome was more stable than that in solution at 40℃ and 60℃. The half lives of amphotericin B in liposome and solution were 1,532.8d and 27.8d at 40℃, but 17. 9d and 8.2d at 60℃, respectively. Conclusion The liposome can improve the light and thermal stabilities of amphotericin B significantly.