Preparation And Properties Of Injectable Poly(N-Isopropylacrylamide)Hydrogels

Due to the strong hydrophilicity, good flexibility and response to outer stimuli, environmental-sensitive hydrogels can be widely used in many fields, such as sensor, drug control-release system. However, the micromolecular crosslinkers used for hydrogel preparation are usually toxic, and the highly crosslinked polymer networks are difficult to degrade. Therefore, it is very important to create nontoxic and biodegradable hydrogels with environmental sensitivity. In this research, based on molecular design and "aldehyde-hydrazide crosslinking" method, injectable and biodegradable hydrogels with environmental-sensitivity was prepared by crosslinking between aldehyde groups on oxidized starch, which is used as biodegradable macromolecular crosslinker, and hydrazide groups on thermosensitive poly(N-isopropylacrylamide) copolymer at room temperature. The main work and results are as follows.(1) Thermosensitive poly(N-isopropylacrylamide) copolymer with hydrazide groups was synthesized by two steps. Firstly, using N-isopropylacrylamide (NIPAM) as main monomer, and acrylic acid (AA) as functional comonomer, three kinds of poly(N-isopropylacrylamide) copolymer, poly(NIPAM-co-AA), with different amounts of carboxyl groups were prepared by solution radical polymerization in ethyl alcohol. Secondly, poly(N-isopropylacrylamide) copolymer with hydrazide groups, poly(NIPAM-co-AA)-hdz, was obtained successfully by dehydration-condensation reaction between hydrazide groups on adipic dihydrazide and carboxyl groups on side chains of poly(N-isopropylacrylamide) copolymer. Carboxyl group content of poly(NIPAM-co-AA) and poly(NIPAM-co-AA)-hdz were measured by conductometric titration in order to calculate the conversion of carboxyl groups transformed to hydrazide groups. In addition, structure of polymers was characterized by IR spectrum.(2) Three kinds of oxidized starch with different amounts of aldehyde groups were prepared by using biodegradable corn starch with low molecular weight as raw material and sodium metaperiodate as oxidized agent. Content of aldehyde groups was measured by conductometric titration in the existence of hydroxylamine hydrochloride and structure of polymer was characterized by IR spectrum too.(3) Based on "aldehyde-hydrazide crosslinking" technic, injectable and biodegradable hydrogels with temperature-sensitivity were prepared by using nontoxic and biodegradable dialdehyde starch as macromolecular crosslinker. Swelling, degradability and drug control-release behaviour of hydrogels with different crosslinking densities were investigated in detail. IR spectrum was used to characterize the structure of the crosslinked polymer. Results indicated that hydrogels possess high swelling ability, good drug load capacity and drug sustained-release property. Experiments demonstrated that hydrogels can response to temperature stimuli and can hydrolyze by acid catalysis, including degradation of starch and hydrolysis of hydrazone bonds. With increasing crosslinking density, degradation rate of hydrogels decreased.