Controlled release of 5-fluorouridine from radiation-crosslinked poly(ethylene-co-vinyl acetate) films

Abstract

The effect of γ-radiation doses of 12.5-380 kGy on the infrared spectra, gel content, mechanical properties, and the release of oxobutyl-5-fluoro-2′-deoxyuridine (OfdUrd, an antitumor agent) from poly(ethylene-co-vinyl acetate) (EVA) films was studied. The results showed that the application of radiation doses produced a crosslinking reaction leading to a maximum gel content of about 85% in the case of 150 kGy. Higher doses did not increase the gel content in EVA films. The mechanical properties (tensile strength, percentage elongation at break and Young's modulus) of all studied EVA matrices were affected by the exposure to γ-radiation. Irradiation doses over 50 kGy caused an increase in the Young's modulus of EVA and at the same time a decrease in the strain per cent. Moreover, the network structure formed after irradiation reduced significantly the OFdUrd release from EVA films. In this manner, the radiation dose applied to the polymeric matrix modulated the release of OFdUrd, avoiding the high concentrations that may cause severe systemic toxicity. The loading of OFdUrd to EVA film triggered a slight hyperemia after implantation, while the inflammatory reaction was only observed during the first two days.