Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain; Instituto Universitario de Farmacia Industrial, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
Int J Pharm. 2015 Oct 15;494(1):17-22. doi: 10.1016/j.ijpharm.2015.08.003. Epub 2015 Aug 6.
The aim of this work is to study the micelle systems of amphotericin B (AmB) and surfactant sodium deoxycholate (NaDC) as possible formulations to treat brain fungal infections. Fungizone(®) and Ambisome(®) were used as AmB references. The particle size, aggregation state, toxicity and efficacy of AmB:NaDC micelles were studied with increasing proportions of NaDC. Differences in the size and aggregation state of the reference formulations and micellar NaDC formulations might explain the differences in their distribution and therefore in their toxicity and efficacy. AmB:NaDC 1:0.8 and 1:1.5 nano-sized micelle systems showed a poly-aggregated form of AmB and small mean particle size (450-750 nm). The AmB:NaDC 1:0.8 and AmB:NaDC 1:1.5 micelle systems studied showed an 8-fold lower toxicity than Fungizone(®). Efficacy was examined in a murine candidiasis model by determining the survival rate and tissue burden reduction in kidneys and brain. The AmB:NaDC 1:1.5 micellar system at 5mg/kg of AmB and the highest amount of NaDC (7.5 mg/kg) presented a good survival rate, and induced a major clearance of brain infection. The new AmB:NaDC 1:1.5 nano-sized micelle system is a promising formulation with a good efficacy/toxicity ratio, which can be attributed to its particle size, AmB aggregation state and NaDC content.
本工作旨在研究两性霉素 B (AmB) 和表面活性剂脱氧胆酸钠 (NaDC) 的胶束系统，作为治疗脑部真菌感染的可能制剂。 Fungizone(®) 和 Ambisome(®) 被用作 AmB 的参考制剂。随着 NaDC 比例的增加，研究了 AmB:NaDC 胶束的粒径、聚集状态、毒性和疗效。参考制剂和胶束 NaDC 制剂的大小和聚集状态的差异可能解释了它们分布的差异，从而解释了它们的毒性和疗效的差异。AmB:NaDC 1:0.8 和 1:1.5 纳米胶束系统显示出 AmB 的多聚聚集形式和较小的平均粒径（450-750nm）。研究的 AmB:NaDC 1:0.8 和 AmB:NaDC 1:1.5 胶束系统的毒性比 Fungizone(®)低 8 倍。通过确定存活率和肾脏和大脑组织负荷减少，在小鼠念珠菌病模型中检查了疗效。以 5mg/kg 的 AmB 和最高量的 NaDC（7.5mg/kg）的 AmB:NaDC 1:1.5 胶束系统呈现出良好的存活率，并诱导了大脑感染的主要清除。新型 AmB:NaDC 1:1.5 纳米胶束系统是一种具有良好疗效/毒性比的有前途的制剂，这归因于其粒径、AmB 聚集状态和 NaDC 含量。
