UCL School of Pharmacy, University College London, London, UK.
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
Nanomedicine. 2017 Jul;13(5):1773-1783. doi: 10.1016/j.nano.2017.02.003. Epub 2017 Feb 16.
Commercially available amphotericin B (AmB) formulations are limited by cytotoxicities, lower efficacies, shelf-life related issues and high production costs. In this study, AmB complexes based on poly(gamma-glutamic acid) (PGGA) were prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone) and liposomal AmB (AmBisome). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40 nm) with a negative zeta potential (-45.5 to -51.0 mV), water-soluble, stable in solution (up to 4 weeks, at 4 °C and 25 °C), and have a high drug loading (up to 35% w/w). In vitro, AmB/PGGA complexes exhibited a more favorable cytotoxicity profile than Fungizone but comparable to AmBisome, with respect to the hemolytic activity and the modulation of pro-inflammatory cytokines (TNF-α and IL-1ß). In-vivo, AmB/PGGA complexes were significantly more efficacious than both Fungizone and AmBisome against experimental murine candidiasis. These results provide strong evidence that AmB/PGGA complexes display better efficacy and safety features than the currently approved AmB products.
市售两性霉素 B（AmB）制剂受到细胞毒性、低疗效、保质期相关问题和高生产成本的限制。在这项研究中，制备了基于聚（γ-谷氨酸）（PGGA）的 AmB 复合物，并评估了它们对两性霉素 B-去氧胆酸盐（Fungizone）和两性霉素 B 脂质体（AmBisome）的疗效。物理特性表明，AmB/PGGA 复合物为纳米级（20-40nm），具有负 zeta 电位（-45.5 至-51.0mV），水溶性好，在溶液中稳定（长达 4 周，在 4°C 和 25°C），载药量高（高达 35%w/w）。体外实验中，与 Fungizone 相比，AmB/PGGA 复合物具有更有利的细胞毒性特征，但与 AmBisome 相当，溶血活性和促炎细胞因子（TNF-α和 IL-1β）的调节也是如此。体内实验中，AmB/PGGA 复合物对实验性念珠菌病的疗效明显优于 Fungizone 和 AmBisome。这些结果有力地证明了 AmB/PGGA 复合物比目前批准的 AmB 产品具有更好的疗效和安全性。
