School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.
Shanghai Haohai Biological Technology Co., Ltd., Shanghai, 200052, PR China.
Colloids Surf B Biointerfaces. 2018 Dec 1;172:372-379. doi: 10.1016/j.colsurfb.2018.08.016. Epub 2018 Aug 10.
Amphotericin B (AmB) is a widely used polyene antifungal agent; however, its poor solubility limits its clinical application. In this study, AmB nanosuspensions were prepared by a high pressure homogenization method (AmB-HPH) and an antisolvent precipitation method (AmB-AP) to improve the drug solubility. To reveal the distinct influences of these two different preparation methods, systematic comparisons of particle size, crystalline state, wettability, in vitro dissolution and in vivo pharmacokinetics on the properties of AmB-HPH and AmB-AP were performed. The results indicated that AmB-AP was in an amorphous state, exhibiting higher saturation solubility and dissolution rate than those of AmB-HPH in the crystalline state. However, the relative bioavailability of AmB-HPH was higher than that of AmB-AP in vivo, which was likely attributed to its better stability. In conclusion, both AmB-HPH and AmB-AP can enhance the solubility and bioavailability of AmB, but the stability of the nanosuspension prepared by the anti-solvent precipitation method should be carefully considered.
两性霉素 B（AmB）是一种广泛应用的多烯类抗真菌药物；然而，其较差的溶解度限制了其临床应用。在本研究中，通过高压匀质法（AmB-HPH）和反溶剂沉淀法（AmB-AP）制备两性霉素 B 纳米混悬剂，以提高药物的溶解度。为了揭示这两种不同制备方法的显著影响，系统比较了粒径、晶型、润湿性、体外溶出度和体内药代动力学对 AmB-HPH 和 AmB-AP 性质的影响。结果表明，AmB-AP 呈无定形态，具有比晶型 AmB-HPH 更高的饱和溶解度和溶解速率。然而，体内 AmB-HPH 的相对生物利用度高于 AmB-AP，这可能归因于其更好的稳定性。总之，AmB-HPH 和 AmB-AP 均可提高两性霉素 B 的溶解度和生物利用度，但应仔细考虑反溶剂沉淀法制备的纳米混悬剂的稳定性。
