Gelatin microsphere-alginate hydrogel combined system for sustained and gastric targeted delivery of 5-fluorouracil

Abstract

In the current study, novel gelatin microspheres/methacrylated alginate hydrogel combined system (5-FU-GELms/Alg-MA) was developed for gastric targeted delivery of 5-fluorouracil as an anticancer agent. While water-in-oil emulsification method was used for the production of 5-FU-GELms, Alg-MA was synthesized through methacrylation reaction occurred by epoxide ring-opening mechanism. Then, 5-FU-GELms/Alg-MA hydrogel system was fabricated by the encapsulation of 5-FU-GELms into Alg-MA hydrogel network via UV-crosslinking. To evaluate applicability of fabricated 5-FU-GELms/Alg-MA as gastric targeted drug delivery vehicle, both swelling and in vitro drug release experiments were carried out at pH 1.2 medium resembling gastric fluid. Compared to drug release directly from 5-FU-GELms, 5-FU-GELms/Alg-MA hydrogel system showed more controlled and sustained drug release profile with lower amount of cumulative release starting from early stages, since hydrogel matrix created a barrier to the diffusion of 5-FU included in microspheres. Drug release kinetic results obtained by applying various kinetic models to release data showed that the mechanism of 5-FU release from 5-FU-GELms/Alg-MA hydrogel system is controlled by Fickian diffusion. All results revealed that 5-FU-GELms/Alg-MA hydrogel integrated system could be potentially utilized as gastric targeted drug carrier to enhance therapeutic efficacy and reduce systemic side effects in gastric cancer treatments for future studies.