Synthesis,Properties And Application Of Double Responsive Hydrogel Based On Oxidized Dextran And Aniline Tetramer

Hydrogel is a kind of polymeric material with a wide range of biomedical uses.Among them,injectable hydrogel has many advantages,such as good biocompatibility and strong drug-loading ability.In comparison with traditional injectable hydrogel materials,the new smart hydrogel carrier material can respond to the external stimuli.Injectable hydrogel drug delivery system with electrical stimuli responsiveness can not only be controlled by electric field,but also avoids the painful invasive surgery,which implant electronic drug delivery devices,instead.A pH-responsive gel drug carrier can respond to the acidic and alkalic changes of the surrounding environment.In this paper,we used the biocompatible dextran and the electrically active aniline tetramer as starting materials.The dextran was firstly converted into oxidized dextran containing aldehyde groups.Furthermore,the electroactive monocarboxyaniline tetramer was grafted onto the main chain of dextran to get an electroactive aniline tetramer grafted copolymer.In order to obtain better cross-linking performance,we designed and synthesized 3,6,9-trioxadecane-1,11-dioxyamine with bis-amine structure,which served as a crosslinking agent.An intelligent dual-reactive electroactive hydrogel carrier material having electrical stimulation responsiveness and pH sensitivity with a hydrazone bond as a crosslinking point was successfully prepared.We have carried out detailed characterization on the oxidized dextran,monocarboxyaniline tetramer,graft copolymer,3,6,9-trioxo-undecane-1,11-dioxyamine,which proved that their structure was consistent with the target product of the original chemical design,and the synthesized materials were electrically active.The gel time,rheology,morphology,pH response of in vitro drug release,in vitro biocompatibility and electrical stimulation responsiveness,and in vivo injectability of the obtained smart hydrogels were characterized.In order to exam the release behavior and effect of the gel on the encapsulated drug,we carried out the encapsulation of the model drug amoxicillin.The in vitro drug release experiments of hydrogels in PBS solutions with different pH values(pH = 7.4 and 5.5)demonstrated that the dual responsive hydrogels have better pH response release ability to amoxicillin drugs.The introduction of the aniline tetramer enable hydrogel to responded to electrical signals.When electrical stimulation is applied,the rate of proliferation of cells on hydrogel is significantly increased.In addition,we tested the cytotoxicity of hydrogels using PC12 cells and demonstrated that the prepared hydrogels have good cytocompatibility.The injectability of the hydrogel was further confirmed by subcutaneous injection of hydrogel into rats.The intelligent dual-response hydrogel drug-loading system prepared in this work can respond to environmental pH and electrical stimulation to achieve controlled release of drugs,and has a good prospect of clinical application...