Synthesis And Properties Of Novel Biodegradable Amphoteric Ph-sensitive Hydrogels

A novel type of amphoteric pH-sensitive hydrogel was designed and synthesized from butanediamine (BDA) and ethylenediaminetetraacetic dianhydride (EDTAD) with amino terminated poly(ethylene glycol) of M w=500 (ATPEG500) as a crosslinking agent, aiming to develop a biodegradable and biocompatible pH-responsive hydrogel. The chemical structures of this hydrogel were characterized by means of chemical analysis, NMR (Nuclear Magnetic Resonance), FTIR (Fourier Transform Infrared) and SEM (scanning electron microscope).The swelling kinetics and pH sensitivity were studied. At last, the degradation of the obtained hydrogel was preliminarily investigated.The main works and conclusions are included as follows:(1) The novel hydrogel with pendent carboxyl groups (PEB-ATPEG500-COOH) was designed and synthesized. Firstly, butanediamine (BDA) reacted with Ethylenediaminetetraacetic dianhydride (EDTAD) through N-acylation ring-opening polymerization of anhydride groups to give a linear copolymer with pendant carboxyl groups (PEB-COOH); then the carboxyl groups in PEB-COOH were activated by N- hydroxysuccinimide (NHS) and dicyclohexylcarbodiimide (DCC) and thereafter cross- linked with ATPEG500, yielding the desired network polymer (PEB- ATPEG500- COOH).(2) NMR, FTIR and SEM analysis showed the successful synthesis of PEB-COOH and PEB-ATPEG500-COOH.(3) The number-average molecular weight ( M n) of PEB-COOH was detectioned by the ninhydrin reaction. The results indicated that changing polymerization conditions could controlled M nof PEB-COOH.(4) pH sensitivity tests indicated that this hydrogel demonstrated three pH sensitive zones at pH 2-4, pH 6-7 and pH 10-11, respectively, suggesting typical amphoteric hydrogel characteristics. The pH sensitivity of the hydrogel was blunted with increasing crosslinking agent amount.(5) The swelling kinetics of in media of pH 2, 7 and 11 were investigated. The results revealed that the swelling is controlled by Fickian diffusion mechanism when pH is 7. However, when pH=2 and 11, anomalous diffusion mechanism dominates the swelling. This transition from Fickian diffusion to anomalous diffusion may be attributed the strong electrostatic repulsion at pH=2 and 11, and thus enhanced chain rigidity and slowed chain relaxation.(6) Ionic strength sensitivity tests indicated that PEB-ATPEG500-COOH is moderately sensitive to ionic strength, and has good salt-resistance.(7) The biodegradability of PEB-ATPEG500-COOH was examined at 37±0.5°C with PBS (pH=7.4, I=0.01) as the medium. Swelling ratios and weight loss ratios were employed to characterize the degradation. The results revealed that the hydrogels exhibited a weight loss ratio of less than 30% in 98 days, suggesting a slow degradation rate.