Preparation Of Thermo-responsive Chitosan-based Hydrogel And Investigation Of Its Properties

Polymer hydrogel refers to a functional polymer material with three-dimensional network structure that can quickly absorb and maintain a large amount of water but is insoluble in water.It is a type of functional polymer material that can absorb water,maintain water,and sustained release so is developing rapidly.Among the natural polymer materials,chitosan has good biocompatibility and biodegradability,and is widely used in the fields of drug delivery and tissue engineering.Thermo-sensitive,injectable,and biodegradable methacrylated hexanoyl glycol chitosans(GM-HGCs)were synthesized to overcome the barriers such as low mechanical properties.The aqueous solution of GM-HGC exhibited solution state at low temperature and converted into hydrogel state at body temperature by thermo-sensitive hydrophobic interaction.The mechanical strength and internal three-dimensional network could be adjusted by the degree of methacrylation and UV exposure time.In vitro cytotoxicity indicated that GM-HGCs exhibited no significant biological toxicity.In vitro drug release studies showed that physical and chemical dual-crosslinking GM-HGCs hydrogels showed sustained release behavior of the anticancer drug gemcitabine,the drug release amount over 93%,and the release time could reach 96 h.All the promising results showed that the photo crosslinkable GM-HGCs could be used as a new thermogelling biomaterial for drug delivery.Poloxamer hydrogel is also a thermo-sensitive hydrogel with good adhesion and biocompatibility.However,poloxamer has so large dependence on concentration that gelation can occur only at a concentration of 15.0%～30.0%.Poloxamer hydrogel degrades quickly and has poor stability in the body,which limits the drug delivery during treatment.In order to decrease the gelatinization concentration and improve drug release properties of poloxamer at body temperature,a thermo-sensitive N-acetyl glycol chitosan/poloxamer composite hydrogel was prepared by complexing N-acetyl glycol chitosan with poloxamer 407(NAGC/P407).The NAGC/P407 solution showed reversible thermo-sensitive sol-gel transition behavior,and the sol-gel transition temperature was well controlled in the range of 25℃～37℃ by regulating the ratio of NAGC/P407,which shortens the gelatinization time(382s)and the concentration.In addition,the NAGC/P407 hydrogel showed sustained release behavior of the anticancer drug gemcitabine,the drug release amount over 93%,and the release time of the drug-loaded gel could reach 72 h.NAGC/P407 composite hydrogel showed the potential for biomedical application as injectable drug delivery carrier.