Preparation And Properties Of Acylated Glycol Chitosan Thermo-Sensitive Hydrogels

Hydrogels are a three-dimensional network structure formed by chemical or physical cross-linking of macromolecules,and through the interaction with water molecules,they absorb water and swell but don’t dissolve.Hydrogels possess excellent physicochemical properties,such as thermal insulation,high specific surface area,air permeability,and designable mechanical and optical properties,which can be applied in biomedical fields such as drug delivery and tissue engineering.Synthetic materials for hydrogels include natural polymers and synthetic polymers.Natural polysaccharides are widely used in the field of biomedicine due to their biocompatibility and biodegradability.Chitosan is a polysaccharide containing a large number of free amino groups.Therefore,a variety of chitosan derivatives were synthesized by modifying the functional groups on the chitosan chain.As a water-soluble chitosan derivative,glycol chitosan(GC)has attracted the attention of researchers in the fields of drug carriers and tissue engineering.In this work,water-soluble glycol chitosan(GC)was selected as the matrix.Acetylated GC(AC-GC)was successfully synthesized using acetic anhydride in mild conditions.The degree of acetylation(DA)was modulated from 27.55% to 86.42% by varying the feed ratio of acetic anhydride to the glucosamine residue of GC.By the introduction of hydrophobic acetyl groups on the backbone of GC,it was not only found that such derivatization would improve the solubility in organic solvents and in vitro biodegradability of GC,but also import new attractive properties such as self-assembling and thermo-sensitive sol-gel transition properties,which may be employed in anti-cancer drug delivery system and injectable drug delivery system.AC-GC self-assembled into nanoparticles in aqueous media with a diameter of 187.9 nm and unimodal size distribution.Furthermore,AC-GC dissolved in PBS(7 wt%)exhibited thermo-sensitive sol-gel transition at 37 ℃.These results suggested that AC-GCs with thermo-sensitive sol-gel transition properties may be employed as a more versatile functional material for biomedical applications.With the goal of extending the use of GC in drug delivery system,the heptanoylated glycol chitosan(HAGC)with different heptanoyl degree(DS)were synthesized by acylation modification through amide coupling reaction between heptanoic anhydride and amino groups on the molecular chain of GC.Thus,the physically cross-linked thermosensitive heptanoylated glycol chitosan hydrogels were prepared.HAGC hydrogels could undergo sol-gel phase transition in response to ambient temperature changes.HAGC(3wt%)dissolved in PBS exhibited sol-gel phase transition behavior at 37 ℃,and its gel concentration was lower than that of AC-GC.By changing the heptanoyl degree and solution concentration of HAGC,the sol-gel transition temperature of HAGC hydrogel could be effectively adjusted.The HAGC hydrogel exhibited a three-dimensional porous structure.As the heptanoyl degree increase,the crosslink density of the HAGC hydrogel increased,the swelling ratio decreased,and the drug release rate slowed down.The HAGC hydrogel showed sustained release effect on gemcitabine,and the drug release time could reach 5 days,and the drug release rate was 70%～91%.Therefore,HAGC hydrogel exhibited important application value in biomedical fields such as drug injection and sustained-release carrier due to its excellent temperature-sensitive properties.