Study On Synthesis And Properties Of Novel Biodegradable PH-sensitive Hydrogels

Two series of hydrogels were designed and prepared using ethylene -diaminetetraacetic dianhydride (EDTAD) and butanediamine (BDA) as main reactants, aiming to develop novel hydrogels for biomedical applications integrating such advantages as pH sensitivity, biodegradability and sound biocompatibility. Their chemical structures were characterized by means of chemical analysis, FTIR (Fourier Transform Infred) and 13C NMR (Nuclear Magnetic Resonance), and their swelling behaviors and pH sensitivity by SEM (scanning electron microscope) and swelling ratio detections. Thereafter, the degradation and cytotoxicity of the obtained hydrogels were preliminarily investigated. The main works and conclusions are included as follows:(1) A hydrogel with a large of pendant amino groups and a few of carboxylic groups (BDA-crosslinked-pEDTAD-BDA I) was designed and prepared as follows: firstly, EDTAD reacted with BDA through solution thermal polycondensation, forming a linear copolymer containing many cyclic imide groups (pEDTAD-BDA-Imide); thereafter, the cyclic imide groups in (pEDTAD-BDA-Imide) reacted with BDA (here BDA was used as a crosslinking agent) to form the final product BDA -crosslinked-pEDTAD-BDA I. The effect of the amount of BDA as a crosslinking agent on the swelling behaviors was investigated.①FTIR, 13C NMR and SEM analysis showed the successful synthesis of pEDTAD-BDA-Imide and BDA-crosslinked-pEDTAD-BDA I.②The swelling experiments indicated that the swelling ratios of BDA -crosslinked-pEDTAD-BDA I reduced with increasing amount of the crosslinking agent BDA and the swelling rate increased with elevating temperature.③pH sensitivity tests suggested that BDA-crosslinked-pEDTAD-BDA I hydrogel could respond to pH variation of the media. In particular, between pH value of 2 and 3, the hydrogel demonstrated the greatest and sharpest swelling ratio jump.④The biodegradability of BDA-crosslinked-pEDTAD-BDA I was examined (PBS as medium, pH=7.4, T=37.0±1℃). The results revealed that the weight loss of hydrogel was linearly increased with time. This linear degradation rate is potentially beneficial to drug release with constant releasing rate.⑤The cytotoxicity of BDA-crosslinked-pEDTAD-BDA I was evaluated by means of both direct contact method and extract method. The results indicated that the hydrogel has no significant cytotoxicity and shows sound biocompatibility.(2) Another hydrogel containing only pendant carboxyl groups (BDA-crosslinked-pEDTAD-BDA II) was designed and prepared as follows: firstly, EDTAD reacted with BDA through N-acylation ring-opening polymerization of anhydride groups to give a linear copolymer with pendant carboxyl groups (pEDTAD-BDA); pEDTAD-BDA was then crosslinked with BDA with dicyclohexylcarbodiimide (DCC) as a condensing agent, producing the desired network polymer BDA-crosslinked-pEDTAD-BDA II.①FTIR and 13C NMR verified the successful synthesis of pEDTAD-BDA and BDA-crosslinked-pEDTAD-BDA II.②The ninhydrin reaction was employed to determine the number-average molecular weight ( M n) of pEDTAD-BDA. The results indicated that M n of pEDTAD-BDA could be controlled by changing polymerization conditions.③pH sensitivity tests suggested that BDA-crosslinked-pEDTAD-BDA II hydrogel could respond to pH variation of the media. In media with a pH value of 3 and 7, BDA-crosslinked-pEDTAD-BDA II showed small swelling ratios; however, in media of pH=12, its swelling ratio suddenly increased, exhibiting sharpest pH sensitivity.