Preparation And Characterization Of The Thermosensitive Hydrogels Composed Of MPEG-grafted Chitosan

Objective: Thermosensitive hydrogel is a kind of intelligent polymeric materials, which undergo a sol-to-gel transition in response to temperature changes. The aqueous phases of these copolymers exhibited thermoreversible transitions from a liquid-like sol at low temperature to a solid or semi-solid gel at high temperature.When its gelation temperature is about 37℃, it can suit to serve as an injectable depot for sustained drug delivery and is potentially suited for a wide range of in vivo biomedical applications.In this thesis,we have synthesized the thermosensitive hydrogel mPEG-grafted chitosan by grafting an appropriate amount of methoxy poly(ethylene glycol) onto the chitosan backbone,studied its chemical and physical properties, and explored drug release in vitro using bovine serum albumin (BSA) as a model protein,which provides a theoretical basis for the controlled-release carrier of protein.Methods: Prepare mPEG-CHO by oxidation of PEG with DMSO/acetic anhydride, and then synthesize mPEG-g-chitosan copolymer by grafting mPEG-CHO onto the chitosan backbone with NaBH₃CN reduction. The samples molecular changes were investigated by 1H NMR and Fourier transform infrared spectroscopy (FT-IR). The grafting ratio of the copolymers was surveyed and evaluated by thermogravimetric analyzers (TGA).1.5%,2.0%,2.5%,3.0% concentration of hydrogel solution was prepared by making the copolymer dissolve in PBS(pH7.2), and examine gel temperature and time by rheometer. Finally,the drug controlled-release behavior in vitro was studied by using mPEG-g-chitosan hydrogels as a drug carrier and BSA as a model protein.Results: The experimental results showed that the grafting rate increased with increase of the mPEG/chitosan, and decreased as NaCNBH₃/mPEG molar ratio increased within a certain range. mPEG-g-chitosan is a temperature sensitivity hydrogel, the gel temperature of the grafted copolymer solution is related to its concentration. mPEG-g-chitosan with 68% of mPEG grafted ratio underwent an apparent sol-to-gel transition in the solutions with polymer concentrations ranging from 1.5 to 2.5 wt.%. Below the transition temperature,the solutions were viscous liquids that flowed easily. As the solutions were heated to body temperature, they transformed into gels.Gel thermosensitive behavior was influenced by the solution concentration. The higher the aqueous solution concentration, the greater the viscosity,the stronger the gel intensity,the lower gel temperature, the shorter the gel time.The transformation from solution to hydrogel is a reversible process,and the gels reverted back to solutions when the temperature dropped to 4℃. The results of drug release in vitro show that, in the solution of PBS at 37℃,BSA model protein was released slowly from the hydrogel carrier,but the release profiles exhibited a fast release rate in the initial hours,followed by a slower release rate with the time going.The release of BSA was thought to be largely dominated by diffusion and gel degradation,the BSA release rate had positive correlation with the acceleration of gel erosion,at the same time,which has associated with temperature,solution concentration of the mPEG-g-chitosan hydrogel.Conclusion: The mPEG-g-chitosan copolymer hydrogels with good properties are prepared by graft copolymerization method. The hydrogels are liquid sol at low temperature, and solid gel at body temperature, the thermosensitive behavior of mPEG-g-chitosan hydrogel is closely related with its concentration.Its polymer concentrations ranging from 1.5 to 2.5 wt.% can transform into gel rapidly near body temperature,and it has a good performance on sustained release protein drugs.The hydrophilic interaction of mPEG branched-chain can protect the protein activity, which significantly increased the cumulative release rate of active protein.The experiment provides a suitable carrier for the safe incorporation and controlled release of many bioactive protein drugs.