Fabrication of alginate-based stimuli-responsive, non-cytotoxic, terpolymric semi-IPN hydrogel as a carrier for controlled release of bovine albumin serum and 5-amino salicylic acid

Herein, we report a functionalized alginate(Alg)-based terpolymeric semi-interpenetrating (semi-IPN) hydrogel, synthesized via free radical polymerization for the delivery of bovine albumin serum (BSA) and 5-amino salicylic acid (5-ASA). To improve mechanical properties, and to modulate surface morphology of Alg, 2-hydroxyethyl acrylate (HEA) was grafted on alginate and then crosslinked using poly(ethylene glycol) diacrylate (PEGDA). The probable structure and compositions of the synthesized semi-IPN terpolymer were identified by FTIR, ¹ H-HR-MAS NMR, and TGA analyses. Achievement of equilibrium swelling state (ESS) and higher elastic modulus values confirmed terpolymer gel formation in aqueous media. Differences in the ESS of the prepared gel at pH 2.5 and 7.4 signify its stimuli-responsive behaviour. The influence of PEGDA on swelling, mechanical properties, surface morphology, cell viability and proliferation, and BSA and 5-ASA delivery were characterized. SEM images show that higher % PEGDA resulted in smaller sized pores in the gel network. Texture analyses demonstrate that hardness, adhesiveness and chewiness of the gel were enhanced at higher PEGDA concentrations. Increases in PEGDA concentration also induced increases in osteoblastic cell viability and higher rates of cell proliferation compared with gels containing lower concentrations of PEGDA. The release results indicate that the gels containing higher concentrations of PEGDA more sustainably release BSA and 5-ASA at 5 days and 30 h, respectively. The experimental data revealed that the synthesized terpolymeric semi-IPN hydrogel may have useful biomedical applications, especially as a carrier of protein (BSA), or 5-ASA (a therapeutic option for conditions of the colon such as Crohn's Disease and Ulcerative Colitis).