Synthesis And Characterization Of Thermoresponsive Hydrogels Cross-Linked With Chitosan

Hydrogels are hydrophilic polymers that are crosslinked to form insoluble, but water-swellable networks. They have been widely applied as controlled drug releasing and tissue engineering materials due to their high water content, flexibility in tailor-made physiochemical properties, and closely resemblance to natural living tissue. Poly(N-isopropylacryamide) (PNIPAAm) is a thermosensitive hydrogel that has received much attention for biomedical use because of its lower critical solution temperature (LCST) behavior at around 32°C in an aqueous solution, which is close to the physiological temperature. In this paper, soluble chitosan was obtained by hydrogen peroxide induced random degradation of the chitosan in the acetic acid solution. Chitosan derivative (N-acryl chitosan, NAC) was synthesized by the acrylation of the amine groups of glucosamine units. The effect of concentration of hydrogen peroxide, reaction temperature and nitrogen protection's on the degradation of the chitosan was investigated. The optimum conditions to prepare the NAC-cross-linker synthesis with the excellent cross-linked ability and water-solubility were obtained. A series of thermoresponsive and degradable poly (N-isopropylacryamide/crylic acid) (P (NIPAAm/AAc)) hydrogels were obtained by redox polymerization with the chitosan derivatives as the cross linker. The lower critical solution temperature (LCST), water content, the thermodynamic and the biodegradable behaviors of P (NIPAAm/AAc) hydrogels were investigated. A preliminary study of the NAC-cross-linked P (NIPAAm/AAc) hydrogels for drug delivery system was performed with model drugs of 5-fluorouracil (5-FU).1,The LCST of hydrogels was significantly influenced by monomer ratio of the NIPAAm/AAc. The LCST increased with increase of the AAc molar ratio, and the amount of the NAC-cross-linker did not influence the LCST and the phase transition behavior of hydrogels evidently.2,The water content of NAC-cross-linked P(NIPAAm/AAc) hydrogels was controlled by the monomer molar ratio of NIPAAm/AAc, swelling media, cross-linking density and the temperature of the media. The swelling ratio of the hydrgels was increased with the increase of AAc content. The water content was higher in water than in other medium. The swelling ratio of the hydrgels was higher at 25°C than at 37°C.3,The thermodynamic stability of the hydrogels was characterized by thermogravimetry. The result showed that the hydrogel had a good thermal stability.4,The deswelling kinetics of NAC-cross-linked P(NIPAAm/AAc) hydrogels were studied. The deswelling rate of the hydrogel was dependent on the content of AAc and NAC-cross-linker.5,The degradation of the NAC-cross-linked P(NIPAAm/AAc) hydrogels as a function of times in the PBS at 37°C were also studied. The break down of the hydrogels was dependent on the cross-linking density, monomer ratio of NIPAAm/ AAc.6,In the subsequent studies, the drugs of 5-fluorouracil (5-FU) was performed with the model of drug delivery system. It was found that the releasing rate and quantity decreased with the increase of AAc content and the cross-linking density in PBS. And the releasing rate and quantity at 37 oC are higher than 25 oC in PBS.