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

• Published in: Macromolecular chemistry and physics 2019-09, Vol.220 (17), p.n/a
• Main Authors: Filipović, Vuk V., Babić, Marija M., Gođevac, Dejan, Pavić, Aleksandar, Nikodinović‐Runić, Jasmina, Tomić, Simonida Lj
• Format: Article
• Language: English
• Subjects: Biocompatibility; biocompatible; Biomedical materials; Cephalexin; degradable; Degradation; drug delivery; Drug delivery systems; Ethylene glycol; Fourier transforms; Free radical polymerization; Free radicals; Glycine; Hydrogels; NMR; Nuclear magnetic resonance; Organic chemistry; pH‐sensitive; poly‐beta amino esters zwitterionic hydrogels; Regeneration; Tissue engineering; Toxicity; Zebrafish; Zwitterions
• ISSN: 1022-1352; 1521-3935
• DOI: 10.1002/macp.201900188

New (β‐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 >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. Novel biodegradable pH‐sensitive poly(β‐amino)ester zwitterionic hydrogels based on natural amino acid glycine are synthesized and characterized. Properties of novel hydrogels can be tuned by varying the amino/diacrylate ratio. All hydrogels exibited excellent viability and proliferation of MRC5 cells. Biocompatibility is confirmed by in vivo acute embryotoxicity assay using zebrafish.