Collect. Czech. Chem. Commun. 2005, 70, 327-338
https://doi.org/10.1135/cccc20050327

Poly(ethylene glycol)-Based Polymer Carrier of Doxorubicin Degradable by Both Enzymatic and Chemical Hydrolyses

Michal Pechar*, Alena Braunov√° and Karel Ulbrich

Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6, Czech Republic

Abstract

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.

Keywords: Drug delivery systems; Cancer therapy; Doxorubicin; Poly(ethylene glycol); Peptide synthesis; Polymer-supported drugs; Antineoplastics; Cytostatics; Biodegradable polymers.

References: 23 live references.