Formulation, pharmacological evaluation, and efficacy studies of occidiofungin, a novel antifungal.

Occidiofungin is a non-ribosomally synthesized cyclic lipopeptide, which possesses broad spectrum antifungal properties at sub-micromolar concentrations. This report explores multiple routes of administration, formulation, and toxicity of occidiofungin in mice. Further, infection studies were performed in mice to assess the application of occidiofungin for treating a systemic yeast and an intravaginal yeast infection. Formulations for intravenous and intravaginal administration of occidiofungin were prepared. Pharmacokinetic analyses were performed in a murine model, and an LCMS method was developed and used to quantify occidiofungin in the mouse plasma samples. Toxicology and histopathology analysis of two repeat dose studies using occidiofungin were performed. In these animal models, following an intravenous administration, liposomal formulation of occidiofungin improved the half-life and peak plasma concentration compared to liposomal-free formulation. Two long-term repeat dosing toxicity studies of occidiofungin indicated the absence of toxicity in organ tissues. A systemic yeast and vulvovaginal yeast murine models of infection were performed. Findings in the systemic infection study has revealed limitations in occidiofungin's use that may be alleviated with the development of novel structural analogs or with further formulation studies. The gel formulation of occidiofungin demonstrated improved efficacy in a vulvovaginal candidiasis study as compared to the commercial product Monistat 3™. This report outlines the optimal routes of administration of occidiofungin and demonstrates minimal toxicity following chronic exposure. Further, the results from these studies provides a clear indication for the use of occidiofungin towards the treatment of recurrent vulvovaginal candidiasis (RVVC), which is a serious and clinically relevant issue.