Retinoids: Formulation development and efficacy evaluation in melanoma cells

Abstract

The effects of retinoids on murine melanoma cells were investigated. The anti-proliferation and anti-metastasis effects of retinoids were tested in cell culture model and tumor model of melanoma. Cyclodextrin-based formulations of retinoids were subsequently developed to improve their solubility, photostability and bioavailability, and molecular modeling was carried out to verify the complexation of retinoids by cyclodextrins. Pharmacokinetic properties of the newly developed cyclodextrin-based formulations were studied in Sprague-Dawley rats. The results showed that the aqueous solubility and photostability of acitretin and 13-cis-RA were dramatically improved by inclusion into cyclodextrins. Findings of the phase solubility studies were consistent with the molecular modeling prediction. In summary, the anti-proliferation and anti-metastasis effects of retinoids were confirmed in B16-F10 cells and experimental lung metastasis model. Cyclodextrin-based formulation of acitretin could improve its oral bioavailability and decrease the variation of its oral pharmacokinetics.