Miconazole nanoemulsions to treat melanoma: formulation development and droplet size and solubility studies

Melanoma is one of the most dangerous skin cancers, with a high mortality rate and an incidence that has increased radically in the past few years. This has led to a huge demand for new more effective forms of treatment. Nanoemulsions have been investigated as potential drug delivery vehicles to target cancer cells, since they are a promising alternative to increase the solubility and skin permeation and retention of hydrophobic drugs.

The purpose of this work was to incorporate miconazole, a hydrophobic antifungal drug with potential anticancer activity, in an oil-in-water (O/W) nanoemulsion for topical administration for the treatment of melanoma. Seventeen O/W nanoemulsions were prepared by spontaneous emulsification. The preconcentrate was constituted by Plurol® Diisostearique, Transcutol® HP and Kolliphor® RH 40, while the aqueous phase was water. A visual examination was performed to confirm the absence of phase separation or heterogeneity. Then an analysis using dynamic light scattering (Zetasizer Nano ZS apparatus) followed, to determine droplet size and polydispersity index (PDI). Nanoemulsions with a PDI below 0.300 and droplet size between 100 – 200 nm were selected for solubility assays. After drug incorporation, at 5 mg/mL, only one out of the seventeen nanoemulsions showed characteristics within the intended parameters.

In conclusion, this study showed that the incorporation of miconazole in nanoemulsions allows to greatly increase its solubility when compared to water (up to 6550 times). Future studies will include determination of viscosity, stability, in vitro drug release, ex vivo drug permeation and in vitro cytotoxicity in melanoma cells.