在增强全身真菌病治疗的前期药物纳米配方中使用"点击"安二B
Dandan Guo1, Changying Shi1, Liye Suo2
1Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
概括
这项研究开发了一种新型的Amphotericin B (AmB) 前药物,使用树突式telodendrimer支架. 新配方显著降低了毒性,并提高了对全身真菌感染的疗效.
科学领域:
- 药用化学 医学化学
- 纳米技术纳米技术
- 菌类学 菌类学是指菌类学.
背景情况:
- 氨酸B (AmB) 对全身真菌感染至关重要,但受到严重毒性和输液相关副作用的限制.
- 像Fungizone®和AmBisome®这样的现有配方具有毒性或疗效限制.
研究的目的:
- 开发一种成本效益高,安全的安福特里辛B配方.
- 为了提高安福特里辛B的治疗指数,用于治疗危及生命的真菌感染.
主要方法:
- 通过酸盐化学,将安福特里辛B与经过酸修饰的树突型端粒体 (TD) 支架结合.
- 安福特里辛B-TD前药物的自我组装成单分散的小粒.
- 在体外和体内对药物释放,细胞毒性,溶血活性和抗真菌功效的评估.
主要成果:
- 优化的安福特里辛B-TD前药物 (AmB-PEG5kBA4) 显示持续释放,由酸性pH和ROS加速.
- 与Fungizone®相比,前体药物表现出较低的细胞毒性和溶血活性.
- 在小鼠模型中,AmB-PEG5kBA4表现出优越的抗真菌疗效和比Fungizone®和AmBisome®更高的最大耐受剂量 (MTD).
结论:
- 这种新型的安福特 B-TD 前药配方为现有治疗方法提供了一个有前途的替代方案.
- 这种方法可以减轻安二B的毒性,同时提高其对全身真菌感染的治疗效果.
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