Poly(ethylene glycol)-based polymer carrier of doxorubicin degradable by both enzymatic and chemical hydrolyses

The synthesis and characterization of a water-soluble biodegradable multiblock polyurethane based on poly(ethylene glycol) blocks interconnected by a pentapeptide derivative N, N'-bis(aspartylprolyl)lysine is described. The pentapeptide linkages are susceptible both to chemical hydrolysis in neutral and mild acid medium (pH 5) and to enzymatic degradation by lysosomal enzyme cathepsin B. Anti-cancer drug doxorubicin was attached to a hydrazide derivative of the polymer via a hydrolytically labile hydrazone bond. Both the pH-triggered hydrolytic release of the drug and the degradation of the polymer carrier by enzymatic and chemical hydrolysis were studied using liquid chromatography.