Preparation Of Disulfide Cross-linked Redox-responsive Hydrogels And Microgels And Their Applications In Drug Controlled Release

Hydrogels are typical materials with three-dimensional network structures, and they show good properties in drug loading and drug controlled release,so they have become a highlight of drug-loaded materials. The three-dimensional network structures of disulfide bonds cross-linked hydrogels can be broken to achieve degradation by using reducing agents like DL-dithiothreitol, glutathione, L-cysteine etc., so the release rate of drug is faster. The presence of the disulfide bonds makes the hydrogels endow with excellent redox-responsive properties of the hydrogels, so the drug which is loaded in the hydrogel can be quickly released in the reducing environment. Research shows that the concentration of reductant glutathione in tumer cells(2~8 mM) is 1000 times more than the normal tissue and cells(1~2 μM), so the significant difference of the concentration of glutathione can be used in reduction controlled release which is crosslinked by disulfide bond in drug delivery system to achieve target release in the tumor tissues and cells. So the hydrogels crosslinked by disulfide bond are the highlights of polymer drug loading system in recent years.In the 1st part of the paper, P(MEO2MA-ss-OEGMA-ss-MAA) migrogels were synthesized by using the monomers of oligo(ethylene glycol) methacrylate(oligo(ethylene glycol) methacrylate(OEGMA) and 2-(2-methoxyethoxy) ethyl methacrylate(MEO2MA), and methacrylic acid(MAA), meanwhile N,N’-Bis(acryloyl) cystamine(BAC) was used as a crosslinking agent in the presence of disulfide bonds, and it synthesized by using precipitation polymerization methods in the absence of any surfactants. That structural units of P(MEO2MA-co-OEGMA) copolymers are temperature responsive, and structural units of PMAA are pH responsive. The microgels of P(MEO2MA-ss-OEGMA-ss-MAA) are spherical and the scanning electron microscope(SEM) shows their diameters are about 400-600 nm. The microgels of P(MEO2MA-ss-OEGMA-ss-MAA) show good temperature-responsive, pH-responsive and redox-responsive properties. This experiment was used doxorubicin hydrochloride as model drug, and the controlled release of drug was triple-responsive(temperature-responsive, pH-responsive and redox-responsive).In the 2nd part of the paper, natural polymer chitosan(CS) was used as the main chain, and the catalysts of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDAC?HCl) and N-hydroxysuccinimide(NHS) were added to activate the carboxyl groups, so that the carboxyl groups of N-acetyl-L-cysteine(NAC) could have amide reaction with amino groups to generate CS-NAC with thiol groups. Thiol groups which are from the macromolecular chains of CS-NAC can slowly oxidize to form disulfide bonds, so CS-NAC are crosslinked to form three-dimensional network structure hydrogels. The disulfide cross-linked CS-NAC hydrogels have good swelling properties and redox-responsive properties to achieve degradation. This experiment was used albumin from bovine serum(BSA) as model drug, disulfide crosslinked hydrogels were fromed and BSA was loaded into these hydrogels at the same time. It had proved that thioled CS hydrogels can realize drug controlled release of the BSA based on redox-responsive propertity.