In this work, nanocomposite hydrogel drug delivery systems based on polyvinyl alcohol and montmorillonite loaded with the capecitabine, as an anti-cancer drug, were developed for oral administration. The gel fraction and swelling ability of the prepared nanocomposite hydrogels were experimentally measured. In vitro release kinetics of capecitabine in nanocomposite hydrogel drug delivery systems were studied. In vitro flow cytometry assay was utilized to exhibit the anti-cancer activity of the prepared nanocomposite hydrogel drug delivery systems against 4T1 cancer cell line. The anti-tumor efficacy of the nanocomposite hydrogel drug delivery systems was also studied in vivo on animal models. The results showed that the amount of montmorillonite incorporated into the nanocomposite hydrogel drug delivery systems could be recognized as a key parameter to adjust the values of the gel fraction, swelling and capecitabine release rate in a manner which by increasing the montmorillonite content, the gel fraction is increased while the swelling and drug release rate are decreased. The flow cytometry results demonstrated the better anti-cancer activity of the capecitabine-loaded nanocomposite hydrogel drug delivery systems as compared with the pure capecitabine. The in vivo assays indicated that the administration of nanocomposite hydrogel drug delivery systems had a significant effect on the reduction of the tumor growth in animal models as compared with pure capecitabine administration. In general, the prepared nanocomposite hydrogel drug delivery systems exhibited a suitable efficacy against 4T1 cancer cell line both in vitro and in vivo and they could be considered as promising candidates for controlled release of anti-cancer drugs in chemotherapy with enhanced therapeutic effects.
Keywords: Nanocomposite hydrogel; cancer; capecitabine; drug delivery system; montmorillonite; polyvinyl alcohol.