Study On Thermo-sensitive And PH-sensitive Poly(N-isopropyl Acrylamide-co-N-hydroxymethyl Acrylamide)/Chitosan Hydrogels For Drug Carrier

The P(NIPAAm-co-NHMAm)/CS hydrogel is obtained by interpenetrating networks (IPN) based on chitosan (CS) and copolymer P(NIPAAm-co-NHMAm) synthesized by N-isopropyl acrylamide(NIPAAm) and N-hydroxymethyl acrylamide (NHMAm). The gelation process, micro-structure characteristics, mechanical and thermo-sensitive properties of the hydrogels were investigated. Meanwhile, the swelling properties, pH-sensitive properties and the drug releasing properties for diclofenac sodium(DS) was further studied, and the swelling kinetics and the drug release kinetics model was established. The main conclusions were obtained as follows:1) The P(NIPAAm-co-NHMAm)/CS hydrogel prepared at10℃is homogeneous, light yellow and transparent gel system with good networks structure. The rheological kinetics shows that its gelation rate is fast, and the presence of CS could prolong the gelation time. The increases of CS content or NHMAm mass ratio can improve the elastic modulus and the maximum compressive stress. The study of light transmittance and DSC show that the lower critical solution temperatures (LCST) of IPN hydrogels raise with the increase of the NHMAm mass ratio. The increase of CS content has little impact on the LCST value, but decreases the degree of thermo-sensitive. When monomer mass ratio(Rw) is11:1, the LCST of hydrogel reached37.8℃, thus the hydrogel can be well applied as a thermo-sensitive drug carrier for human body.2) The monomer mass ratio, CS content, cross-linker content, temperature, pH value, and ionic strength both have the effect on the swelling property of hydrogels. Schott’s second kinetics model can describe the swelling kinetics of hydrigel correctly. With the increase of temperature, the swelling ratio of hydrogels decreases. The swelling ratio increases with reduce of pH value within the scope of1.4～8.0. The result shows that the hydrogels have both pH-sensitive and thermo-sensitive properties. Beside, the IPN hydrogels have fast thermo-responsive speed and good recovery performance, which can meet the application demand for drug released.3) The embedding of diclofenac sodium (DS) in P(NIPAAm-co-NHMAm)/CS hydrogel delivery system has obtained. The influences of monomer mass ratio, CS content, temperature and pH on the drug release properties have been investigated. The result shows that the hydrogels sustained release can reach25hours in the receptor fluid (37.5℃, pH=7.4) when monomer mass ratio is11:1and CS content is0.6%. The release kinetics can well follow the modified first order model.The study in this paper will lay a foundation for a new system of the P(NIPAAm-co-NHMAm)/CS hydrogel applied as drug carrier.