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  • Title: Efficacy and toxicity evaluation of new amphotericin B micelle systems for brain fungal infections.
    Author: Moreno-Rodríguez AC, Torrado-Durán S, Molero G, García-Rodríguez JJ, Torrado-Santiago S.
    Journal: Int J Pharm; 2015 Oct 15; 494(1):17-22. PubMed ID: 26256151.
    Abstract:
    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.
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