Preparation And Characterization Of Chitosan Based Injectable Thermosensitive Hydrogel

Chitosan is a kind of natural, cationic, hydrophilic polysaccharide with non-toxicity and good biocompatibility. Its unique chemical and biological properties make it applicable in the pharmaceutical and biomedical fields as well as in the drug delivery system. There exist difficulties in the widely application of the chitosan because of a lot of hydroxyl groups and aminogroups present in the glycosaminoglycan units of chitosan. These groups constitute the intra-, inter-molecular hydrogen bonds. These hydrogen bonds make chitosan insoluble in water and organic solvents. Thus, various studies were conducted to make water-soluble derivatives of chitosan by chemical modification techniques. Poly (ethylene glycol) is a kind of polyether biopolymer with preferable hydrophilicity and biocompatibility. It can dissolve in water and many other solvents, especially in tissue fluid. It can be eliminated ex vivo without any toxicity. Its good properties can be transferred when poly (ethylene glycol) is conjugated to other substances.From all above, we conjugated PEG via an amide linkage to the plycosaminoglycan units of chitosan. The main contributions of this dissertation are listed as follows:(1) We conjugated PEG via an amide linkage to the plycosaminoglycan units of chitosan. Spectra of Transform Infrared(FTIR) indicated that mPEG-graft-Chitosan was successfully synthesized.(2) Various PEGylated chitosan in different PEGylated degrees were synthesized. The swelling behaviors of various PEGylated chitosan in water were investigated. The more degree of PEG grafted, the more solubility of PEGylated chitosan was.(3) The result of thermosensitive experiments showed that thermosensitive behavior of PEGylated chitosan in water was dependent on the degree of PEG substitution. Only when the degree of PEG substitution was in the range of20%-50%, the aqueous solution displayed thermosensitivity. Meanwhile, the thermosensitivity of PEGylated chitosan hydrogel is highly relative to its concentration.(4) For hydrophobic drug, PEGylated chitosan can be used for controlling the drug release up to over one week.Prolonged release of small molecule drug up to10days was achieved by incorporating the drug in liposome from the hydrogel.(5) PEGylated chitosan aqueous solution performs good biocompatibility and the degree of haemolysis is less than1%without aggregation at1.5h. Subcutaneously injected solution formed a gel in rat within a few minutes and the integrity of gel remained for more than8days. The formed gel retained certain morphology and intense which is enough to be easily removed.PEGylated chitosan hydrogel possesses good thermosensitivity, can form gel in the animal’s body and control drug release. With good biocompatibity, PEGylated chitosan hydrogel is a kind of ideal injectable implant drug carrier.