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

摘要

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, ~(13)C 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 NH_2 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.