Amphotericin B (AmB) is a highly effective polyene antifungal agent typically used for invasive fungal infections. Despite the efficacy of this drug, there are major limitations to its use due to adverse side effects, including acute infusion-related febrile reactions and dose-dependent nephrotoxicity. These effects are attributed, at least in part, to the aggregation of AmB due to its extremely poor water solubility. To overcome this problem, we have designed a novel drug delivery system that harnesses the unique properties of ionic liquids. Ionic liquids are organic cations and anions whose melting point is below 100°C; some of which are remarkably liquid at room temperature. Here, high concentrations of AmB were solubilized in a hydrophilic cholinium-based room temperature ionic liquid, a novel hydrophobic dicationic cholinium-based ionic liquid, and in mixtures of the two. The absorption spectrum of AmB in the ionic liquid, ionic liquid mixtures, and prepared nanoemulsion indicates excellent monomerization. In vivo biocompatibility of the ionic liquids was analyzed using zebra-fish assays and the novel dicationic cholinium-based ionic liquid was characterized using differential scanning calorimetry (DSC). The relative hydrophobicity of the prepared ionic liquids was analyzed using pyrene fluorescence studies. Nanoemulsions of the ionic liquids and ionic liquid mixtures were prepared and in vitro biocompatibility was analyzed using a cell viability assay. Hemolytic activity of the AmB ionic liquid nanoemulsion was analyzed and the antifungal activity of the AmB nanoemulsion formulation was evaluated against Candida Albicans.

Room-temperature ionic liquid based nanoemulsions: Synthesis and formulation for delivery of poorly water soluble active pharmaceutical agents

256th National Meeting (2018)

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