Hydrogels containing 5-Fluorouracil obtained by γ-irradiation. Synthesis, characterization and in vitro release studies

Abstract

The functionalization of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) with glycidyl methacrylate (GMA) gives rise to a water-soluble copolymer PHEA-GMA (PHG) containing double bonds and ester groups in the side chain. Aqueous solutions of PHG alone or in combination with N,N′ methylenbisacrylamide (BIS) have been exposed to a γ-ray source at different irradiation doses in order to obtain polymeric networks. All samples have been prepared both as water-swellable microparticles and as gel systems. Microparticles have been characterized by FT-IR spectrophotometry and swelling measurements in aqueous media mimicking biological fluids. The effect of irradiation dose and BIS presence on rheological behavior of the gel systems had also been investigated. All prepared hydrogels are able to incorporate, during γ-irradiation, 5-Fluorouracil, (5-FU) chosen as a model drug and to release it in simulated biological fluids, as confirmed by the in vitro drug release studies at pH 1 and pH 7.4. Gels of PHG containing 5-FU, obtained in the presence or in the absence of BIS, are able to release this drug in a prolonged way, more slowly than a commercial ointment, as confirmed by in vitro studies at pH 5.5 and pH 7.4 using a Franz diffusion cell system and a synthetic membrane.