In Vitro and In Vivo Biocompatibility of Novel Zwitterionic Poly(Beta Amino)Ester Hydrogels Based on Diacrylate and Glycine for Site-Specific Controlled Drug Release

Abstract

New (beta-aminoester) hydrogels (PBAE) based on di(ethylene glycol)diacrylate and glycine are successfully synthesized and characterized for the first time in this work. PBAE macromers are obtained using Michael addition. By changing the diacrylate/amine stoichiometric ratio, but maintaining it gt 1, samples with different chemical structure containing acrylate end-groups are obtained. The hydrogels are synthesized from macromers utilizing free radical polymerization. Chemical structure of macromers and hydrogels is confirmed by proton nuclear magnetic resonance, and Fourier transform infra-red spectroscopy. Swelling and degradation rates in physiological pH range change notably with pH and monomer molar ratio, validating pH sensitivity and zwitterionic behavior, which can be finely tuned by changing any of these parameters. In vitro cytotoxicity and in vivo acute embryotoxicity in zebrafish (Danio rerio) performed to assess the biocompatibility of the novel hydrogel materials and their degradation products reveal that materials are nontoxic and biocompatible. The Cephalexin in vitro drug release study, at pH values 2.20, 5.50, and 7.40, demonstrates pH-sensitive delivery with the release profiles effectively controlled by pH and the hydrogel composition. PBAE hydrogels exhibit great potential for a variety of biomedical applications, including tissue regeneration and intelligent drug delivery systems.