Based On PEG - Based Polymer Temperature / PH - Sensitive Hydrogel Click Chemistry Synthesis And Properties

Stimuli-responsive hydrogels based on synthetic polymers have potential applications in biomedical and tissue engineering fields, such as drug sustained release, drug carriers, artificial muscle and embedding of active enzyme. Among stimuli-responsive hydrogels, temperature or/and pH responsive hydrogels are most widely investigated because these two factors can be easily controlled and they are very important physiological parameters of human and biological systems.2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) and oligo(ethylene glycol) methacrylate (OEGMA) with oligo(ethylene glycol) side chains have been attracting abroad attention to prepare temperature responsive polymers as PEG analogues. The attractive characteristics of polymers are their water solubility, biocompatibility and nontoxicity. N-hydroxymethylacrylamide (HMAM) is not only a kind of functional monomer with hydroxyl group, but also since HMAM is a hydrophilic monomer, it can also be employed to adjust the LCST of the temperature responsive copolymer. The hydroxyl groups on HMAM chains can be transformed into azide or alkyne groups. Poly(methacrylic acid) (PMAA) as amphiphilic macromolecule has the characteristics of its unique responsiveness to pH and ionic strength, and the pH responsive hydrogels based on MAA have potential applications in the drug conveying system and the carboxyl groups on PMAA can be transformed into alkyne groups.Firstly, the temperature responsive copolymer P(MEO2MA-co-OEGMA-co-HMAM) based on MEO2MA, OEGMA and HMAM was prepared, the hydroxyl groups on copolymer were transformed into azide or alkyne groups respectively, and a temperature-sensitivity self-cross linking hydrogel was prepared by click chemistry among the copolymers P(MEO2MA-co-OEGMA-co-HMAM). Secondly, the pH responsive PMAA was prepared, the carboxyl groups on PMAA being transformed into alkyne groups, and a novel temperature/pH responsive hydrogel was prepared by click chemistry between the azide-P(MEO2MA-co-OEGMA-co-HMAM) and alkyne-PMAA, and the alkyne-PMAA as the a cross-linker. Specific works were as follows:1. A novel temperature responsive copolymer P(ME02MA-co-OEGMA-co-HMAM) was synthesized by atom transfer radical polymerization (ATRP). The copolymer was characterized by FTIR,1H NMR, and GPC. Temperature sensitivity for the copolymer and the effects of salts on the lower critical solution temperature (LCST) of copolymer aqueous solutions were studied by transmittance measurements at different temperatures. Then, the hydroxyl groups on P(MEO2MA-co-OEGMA-co-HMAM) chains were transformed into azide or alkyne groups respectively. A temperature-sensitivity self-cross linking hydrogel was prepared by click chemistry among the copolymers P(MEO2MA-co-OEGMA-co-HMAM). Rheological kinetics of gel formation demonstrated that gelation had commenced within 1 minute, and since then the storage modulus (G’) was higher than the loss modulus (G"). The pore size and swelling ratio of the prepared hydrogels decreased with increasing the temperature because hydrophobic polymer-polymer interactions results in the self-aggregation of PMOH chains at a higher temperature (7>LCST), that proved the formed hydrogel had temperature sensitivities. BSA and anethole respectively were used as a model hydrophilic and hydrophobic drug to examine in vitro the sustained release from hydrogel. Results showed that the anethole release rate from hydrogel at 37℃ was slower than BSA.2. The pH responsive PMAA was synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) and the carboxyl groups on PMAA were further transformed into alkyne groups. The polymers were characterized by FTIR,1H NMR, and GPC. pH sensitivity for the polymers were studied by transmittance measurements at different pH. a novel temperature and pH responsive hydrogel was fabricated by click chemistry between the azide-P(MEO2MA-co-OEGMA-co-HMAM) and alkyne-PMAA in the presence of CuSO4 and sodium ascorbate in aqueous solution. Rheological kinetics of gel formation demonstrated that gelation had commenced within 5 minutes at 25℃, since then G’ was higher than G". SEM images of hydrogel morphology and the swelling ratios of hydrogel under different temperatures and pH proved the formed hydrogel had temperature and pH sensitivities. BSA and anethole respectively were used as a model hydrophilic and hydrophobic drug to examine in vitro the sustained release from hydrogel. Results indicated that the anethole release rate from hydrogel at 37℃ was slower than BSA.