Preparation Of N-isopropylacrylamide-based Thermo-sensitive Injectable Sol-gel System And Study Of Its Properties

Usually, the medical thermo-sensitive injectable hydrogels system undergoessol to gel transition at body condition. Its research of being used in controlled drugrelease and tissue engineering is very active. The ideal thermo-sensitive injectablehydrogels should meet some requirements: low viscosity before injection, shortgelation time and stable gel. At critical concentration, poly(N-isopropylacrylamide)in aqueous solution undergoes sol-gel transition at around32℃. While as injectablegel, there are still some problems, such as, longer gel time, polyNIPAAm undergoesa sol-to-shrunken gel transition when the temperature is raised above its LCST, highcritical gelation concentration and so on. The hydrogels performance of poly(N-isopropylacrylamide) can be adjusted by copolymerizing with hydrophilic andhydrophobic monomers. So the research of Poly(-N-isopropylacrylamide) used incontrolled drug release and tissue engineering is very extensive.A novel N-isopropylacrylamide-based thermo-sensitive injectable sol-gelsystem was prepared with N-isopropylacrylamide(NIPAAm),2-hydroxyethylacrylate(HEA) and2-methoxyethyl acrylate(MEA) and so on by changing thehydrophilic/hydrophobic monomer ratio to adjust the gelation temperature andsensitivity of the copolymer. The main research contents are as follows:1. The copolymer of N-isopropylacrylamide(NIPAAm),2-hydroxyethylacrylate(HEA) and2-methoxyethyl acrylate(MEA)(P(NIPAAm-co-HEA-co-MEA))was prepared by free radical polymerization. The structure, composition, molecularweight and distribution were studied by FT-IR,1H-NMR and GPC respectively.Different concentrations and composition of polymers solution were studied by thetest tube inverting method. Samples with sol-gel transition performance, whose geltemperature, gel time, phase transition time, shrinkage and sol time wereinvestigated. The gel temperature of the samples was also characterized by DSC. Theviscosity of copolymers dissolved in deionized water before/after the transition wasdetermined by hybrid rheometer. The results showed that the composition of thecopolymer had important influence on the gelation temperature (Gelationtemperature) while the concentration of the copolymer almost had no effect on thegelation temperature, the more the content of the hydrophobic segments (MEA)inthe copolymer, the lower the gelation temperature. Gel time and Phase transitiontime shortened with the content of NIPAAm and HEA decreased in the copolymer. P(NIPAAm-co-HEA-co-MEA) had shorter(less than10s) phase transition time (sol toturbid), shorter(less than15s) gel time (sol to gel), longer sol time (gel to sol) andlower shrinkage compared with PNIPAAm.2. The copolymer of2-hydroxyethyl acrylate(HEA) and2-methoxyethylacrylate(MEA)(P(HEA-co-MEA)) was prepared by free radical polymerization. Thestructure, composition, molecular weight and distribution were studied by FT-IR, 1H-NMR and GPC respectively. The solubility of polymers in deionized water andmethanol were studied. The test tube inverting method was employed to study thesol-gel properties of the different composition and concentration of polymers indeionized water, ethanol and water/ethanol solution. The results showed that HEAand MEA had the same reactivity. The more the hydrophilic (HEA) segment was, thebetter the water-soluble of the P(HEA-co-MEA) was. P (HEA-co-MEA) wasthermo-sensitive polymer. But both P (HEA-co-MEA) and the mixture of P(HEA-co-MEA) with PNIPAAm only had phase transition, no sol-gel transitionwhen temperature changed.3. A novel thermo-sensitive and pH-sensitive polyethylene glycol/polyetheramine(PEG/D-2000) hydrogel was prepared with PEG, polyether amine,tri-ethanolamine, hexamethylene diisocyanate when DMF and butanone as solventrespectively by microwave in view of many advantages of microwave heatingtechnology in chemical reation such as uniform heating, rapid reation and so on. Thechemical structure of the PEG/D-2000hydrogel was analyzed with FT-IR. Theeffects of hydrogel strength such as PEG and D-2000ratio, water content werestudied by tensile machine. Weighing method was used to determine the effects ofhydrogel ratio on the thermo-sensitive, pH-sensitive and swelling behavior inethanol/water. The results showed that the tensile strength of the hydrogel increasedwith the PEG ratio decreased while the swelling ratio increased with the PEG ratioincreased. The hydrogel in water was thermo-sensitive and reversible. The biggerswelling was, the better temperature reversible responsiveness was. The hydrogelwas pH-sensitive at pH(1-4).