Novel amphoteric pH-sensitive hydrogels derived from ethylenediaminetetraacetic dianhydride, butanediamine and amino-terminated poly(ethylene glycol): Design, synthesis and swelling behavior

Novel amphoteric pH-sensitive hydrogels with pendant carboxyl and backbone tertiary amine groups were designed and synthesized. First, ethylenediaminetetraacetic dianhydride (EDTAD) reacted with butanediamine (BDA) via N-acylation reaction to give a polyamide prepolymer with pendant carboxyl groups (PEB–COOH); then amino-terminated poly(ethylene glycol) 500 (ATPEG500) was added as a cross-linking agent to produce the desired network polymer (PEB–ATPEG500–COOH). The obtained hydrogels are potentially degradable and non-toxic since its backbone and cross-linking sections are both linked by amide bonds and all monomers have been proved as safe. FTIR, ¹H NMR, ¹³C NMR and ninhydrin reaction method were employed to qualitatively and quantitatively characterize the obtained polymers. The effect of cross-linking agent amount, characterized by the molar ratios (R_m) of NH₂ groups in ATPEG500 to pendant COOH groups in PEB–COOH, on the swelling behavior of the proposed hydrogel was examined. The results indicate that the equilibrium swelling ratio decreases and the pH-sensitivity becomes retarded with the increase of R_m. For PEB–ATPEG500–COOH hydrogels with R_m no more than 0.42, they exhibited three SR_e variation zones at pH 2–4, pH 6–7 and pH 9–11, respectively, suggesting obvious and interesting amphoteric pH-sensitivity. In addition, the swelling kinetics tests on PEB–ATPEG500–COOH with R_m = 0.32 reveal that the swelling kinetics of proposed hydrogel follows a Fickian diffusion process in media of pH 7, and an anomalous diffusion process in media of pH 2 and 11. The above obtained results will facilitate the application of this proposed hydrogel in biomedical fields, particularly in the drug controlled release.