Design and Study of Nanoceria Modified by 5-Fluorouracil for Gel and Polymer Dermal Film Preparation

In this work we studied nanoceria (CeO₂NPs) and nanoceria modified by 5-fluorouracil (5FU) as potential APIs. Nanoceria were synthesized by precipitation in a matrix of hydroxyethyl cellulose or hydroxypropylmethyl cellulose, using cerium (III) nitrate and meglumine. Nanoceria properties were estimated by UV, FTIR and X-ray photoelectron spectra; scanning electron and atomic force microscopy; powder X-ray diffraction patterns and energy dispersive X-ray microanalysis. The cytotoxicity of nanoceria and polymer-protected nanoparticles was evaluated using the established cell line NCTC clone 929 (C3H/An mouse, subcutaneous connective tissue, clone of L. line). The morphology and metabolic activity of nanoparticles at 10 μg∙mL^-1 of cells was not significant. In addition, the cytotoxic effects of nanoceria were assessed on two human colorectal cancer cell lines (HT29 and HCT116), murine melanoma B16 cells and normal human skin fibroblasts. An inhibitory effect was shown for HCT116 human colorectal cancer cells. The IC₅₀ values for pure CeO₂NPs and CeO₂NPs-5FU were 219.0 ± 45.6 μg∙mL^-1 and 89.2 ± 14.0 μg∙mL^-1, respectively. On the other hand, the IC₅₀ of 5FU in the combination of CeO₂NPs-5FU was 2-fold higher than that of pure 5FU, amounting to 5.0 nmol∙mL^-1. New compositions of nanoceria modified by 5-fluorouracil in a polymer matrix were designed as a dermal polymer film and gel. The permeability of the components was studied using a Franz cell.