The Synthesis Of Polymalic Acid And Properties Of Its Derivatives Modified By Methoxypolyethylene Glycol As A Drug Carrier

Polymalic acid is a kind of aliphatic polyester and its structure unit is the malic acidmonomer. PMLA has good water-soluble, biocompatible and biodegradable. Its pendentcarboxyl group can be covalently bound with hydrophobic antineoplastic drugs and othersmall molecule or other polymer to form graft co-polymer. The PMLA derivatives areworthy to use as novel potential biomedical materials. However, the research on thesynthesis of polymalic acid is little, especially the chemical synthesis. So far, all themethods of synthesis of β-polymalic acid are based on β-substituted-β-lactone. so thesynthesis of β-substituted-β-lactone is the key to all of the synthetic steps.We study the synthetic routine of β-polymalic acid and choose a methods of easilyhandling,operating and most economic. the simple synthetic journey is: the raw materialsL-aspartic acid will be transformed to bromosuccinic acid by diazo-reaction，then dehydrated under trifluoroacetic anhydride, then reacted with benzyl alcohol to formmixture of RS-3-benzyloxycarbonyl-3-bromopropanoic acid andRS-2-bromo-3-benzyloxycarbonylpropanoic acid, benzyl-β-malolactonate was achievedvia cyclization reaction. The PMLABz was achieved via ring-opening polymerizationfrom benzyl-β-malolactonate and transform to PMLA through hydrolysis. We studied theyield of4-benzyloxycarbony-l-2-oxetanone(β-substituted-β-lactone) through differentreaction temperatures, time, solvent, and the amount of AgNO3and the optimum yield is33%. The relation between Poly(β-benzyl malate) and initiator also were discussed. Theproduct were charactered by1H NMR，IR，GPC.In order to prepare the methoxypolyethylene glycol-Poly(β-benzyl malate)loading-drug micelle. The synthesis of PMLABz was achieved via ring-openingpolymerization from benzyl-β-malolactonate which achieved from L-aspartic acid thoughtdiazotization reaction and cyclization reaction. Methoxypolyethylene glycol amine wascovalently bound on Poly(β-benzyl malate) and self-assemble to form polymeric micelle.then camptothecin was encapsulated to hydrophobic core. The particle size, entrapmentefficiency, drug loading efficiency, critical micelle concentration were measured bydifferent techniques. The further researches will be continued based on the thesis.