Preparation And Properties Of PH Sensitive Carboxymethyl Chitosan Hydrogels

Aspirin?ASP?is a commonly used antipyretic analgesic.In recent years,clinical trials have found that it also has the effect of anti-platelet aggregation,but long-term high doses can cause a variety of complications.In order to avoid the disadvantages of systemic administration of aspirin by oral administration,local and controlled administration methods are employed to prolong the therapeutic effect and reduce cytotoxicity by maintaining drug release and reducing drug exposure.Carboxymethyl chitosan has many important pharmacological effects and is widely used as a matrix molecule in the field of drug administration.In this experiment,the carboxymethyl chitosan as the research object,through the physical cross-linking of silver particles,aims to reduce the toxicity of the cross-linking process,and further enhance the antibacterial capacity of carboxymethyl chitosan hydrogel;On the other hand,a composite hydrogel composed of carboxymethyl chitosan and micelles is designed and used as a dual drug carrier to broaden its application range.The Ag/AgO/carboxymethyl chitosan hydrogel is prepared by in-situ precipitation under reducing conditions using AgNO₃,a cross-linking agent.The experimental results show that the hydrogel is a smooth,continuous,porous,three-dimensional network structure with pH-sensitive swelling and degradation properties.Aspirin can be controlled in vitro and released slowly.The XPS data fitting analysis revealed that the crosslinked silver mainly exists in the form of elemental Ag and Ag²⁺.The antibacterial experiments of hydrogels against E.coli showed that the higher the content of cross-linker AgNO₃,the stronger the antibacterial performance of hydrogels.The disulfide-bonded hydrophilic segment PEG-SS-COOH polymer was synthesized using dithiodipropionic acid and PEG esterification.The ring-opening polymerization of?-caprolactone in the presence of Ar gas provides a hydrophobic HO-PCL-OH homopolymer.The PEG-SS-PCL-SS-PEG triblock polymer was prepared by reacting the two in a certain proportion and spontaneously assembled into micelles in an aqueous solution.Then,ASP-loaded micelles were dispersed in an Ag/AgO/carboxymethyl chitosan hydrogel network loaded with another hydrophilic drug to form dual drug-loaded Ag/AgO/carboxymethyl chitosan water.By DLS characterization,the micelles have redox sensitivity due to the insertion of disulfide bonds,and there is a certain stability within 24 h in the absence of reducing substances.The in-vitro simulated release test of the composite hydrogel showed that once the composite hydrogel was exposed to a micro-environment with high pH or high DTT concentration,the hydrogel network would swell or degrade,and the micelles would be cleaved,triggering drug release.Due to this particular pH or reduction-induced structural transformation,this hydrogel complex can be a candidate material for on-demand dual drug delivery systems.