Study Synthesis And In Vitro Drug Release Of PGA And GSH Dual-responsive Drug Carrier

At present, cancer is an incurable disease,which is the only second to threat to human life to heart disease. the environment between the cancer cells or tumor cells and normal tissues or cells has the big difference in the body. for example, pH value (6.75) of cancer cells or tumor cells was slightly lower than normal tissue of pH value (7.23).GSH in the tumor cells or cytoplasm is as much as four times, with strong reduction potential, for the research of synthesis of reduction stimuli responsive drug carrier system it provides a theoretical basis.First of all, L-cysteine was selected as the central core, connecting phenylacetyl which is sensitive to PGA enzyme, chlorambucil which is convenient to treat cancer disease and polyethylene glycol(PEG) which can enhance water solubility through stable chemical bonds (amide, phenolic ester, amino ester)at amino,carboxyl and sulfydryl respectively, resulting in the amphiphilic compound which can release chlorambucil triggered by PGA enzyme and GSH. and by1H NMR,13C NMR to its structures have been characterized. The structure of all the compounds were charactered by1H NMR,13C and MALDI-TOF-MASS, and its1H NMR spectrum chart suggests that the target compound shows different patterns in aqueous and organic solutions.Second, component is unitary by gel chromatography (GPC) method; the critical micelle concentration (CMC) was measured to be50mg/L by pyrene fluorescence probe method; Dynamic light scattering (DLS) test result showed that the hydrodynamic diameter was17.5nm; the thermometer test result showed that lower critical solution temperature was55℃.Finally, dithiothreitol (DTT) and PGA enzyme were added to simulate the drug carrier molecules in vitro drug release experiment, the carrier drug molecules released the drug in8h,whose rate was80%; MCF-7breast cancer cells was chosed as experiment materials in vitro cytotoxicity experiment by MTT, the results showed that chlorambucil had obvious toxic to cancer cells under the action of PGA enzyme and GSH. It proved that the drug carrier molecule had dual-signal-responsive carrier to enzame and redox.