Acid sensitive polyethylene oxide - graft - before adriamycin drug synthesis and characterization
|Course||Polymer Chemistry and Physics|
|Keywords||Anionic polymerization Ethylene oxide Allyl glycidyl ether Macromolecular drugs Doxorubicin|
This article by anionic ring-opening polymerization method, and the synthesis of the side chain functional group with a plurality of allyl functional polyethylene oxide (PEO-g-allyl). Allyl-functional groups by chemical modification methods, was converted to a hydrazine bond, then by linking the amine bond with the anticancer drug doxorubicin (DOX) on the carbonylation reaction has an acid-sensitive hydrazone bond, i.e. to give an acid-sensitive The macromolecular drugs PEO-g-DOX. Then study the behavior of the macromolecular drugs acid responsive drug release in vitro release experiments; through cell experiments to study the macromolecular drugs intracellular drug release and cytotoxicity. Through experiments with rats to study the macromolecular drugs in the bio-distribution of the animals. The main contents and results are as follows: (1) synthesis of a series of PEO-g-allyl: first with potassium naphthalene generate the potassium salt of the ethylene glycol is reacted with ethylene glycol, then adding monomer ethylene oxide (EO) and alkylene propyl glycidyl ether (AGE), by anionic polymerization to obtain a random copolymer. This polymer main chain with PEO having the same structure, but with the reactive double bond in a side chain with a plurality. The experimental results show that this reaction is an \And the polymer maintained the PEO good solubility, biocompatibility and other characteristics. (2) through a multi-step chemical modification method PEO-g-allyl side chain double bond is efficiently converted to the diamide bond, PEO-g-HYDRAZINE flexible multi-reaction than the star (DOX), and then with the anticancer drug, and more soft than star carbonyl can hydrazine key reaction of the hydrazone bond, hydrazone bond at pH GT; 7 environment is relatively stable under, but in the environment of pH 5-6 may be so that in the fast fracture anticancer drugs DOX rapid release to achieve the purpose of the release of the stimuli-responsive. The macromolecular drugs inherited PEO in water and a good solubility characteristics, can be quickly dissolved in water. Model to the RAW 264.7 HaLa cells in vitro experiments showed that the macromolecular drugs, cytotoxic. Phagocytosis of the macromolecular drugs within cells using RAW 264.7 cells, the experimental results showed that within 24 hours of the macromolecular drug has been poured into the cell nucleus. The animal cycle experiments show that the macromolecular drugs greatly extended DOX animals cycle time, improve its tumor-targeting performance.