Poly(ethylene glycol) multiblock copolymer as a carrier of anti-cancer drug doxorubicin.

Abstract

The synthesis of a novel water-soluble polymer drug carrier system based on biodegradable poly(ethylene glycol) block copolymer is described in this paper. The copolymer consisting of PEG blocks of molecular weight 2000 linked by means of an oligopeptide with amino end groups was prepared by interfacial polycondensation of the diamine and PEG bis(succinimidyl carbonate). The structure of the oligopeptide diamine consisting of glutamic acid and lysine residues was designed as a substrate for cathepsin B, a lysosomal enzyme, which was assumed to be one of the enzymes responsible for the degradation of the polymer carrier in vivo. Each of the oligopeptide blocks incorporated in the carrier contained three carboxylic groups of which some were used for attachment of an anti-cancer drug, doxorubicin (Dox), via a tetrapeptide spacer Gly-Phe-Leu-Gly. This tetrapeptide spacer is susceptible to enzymatic hydrolysis. In vitro release of Dox and the degradation of the polymer chain by cathepsin B as well as preliminary evaluation of in vivo anti-cancer activity of the conjugate are also demonstrated.

• Authors: M Pechar, K Ulbrich, V Subr, L W Seymour, E H Schacht
• Journal: Bioconjugate chemistry (Bioconjug Chem) 2000 Mar-Apr Vol. 11 Issue 2 Pg. 131-9 ISSN: 1043-1802 [Print] United States
• PMID: 10725088 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Delayed-Action Preparations
• Drug Carriers
• Oligopeptides
• Polymers
• Polyethylene Glycols
• Doxorubicin
• Cathepsin B

Topics

• Animals
• Antineoplastic Agents (adverse effects, pharmacology)
• Cathepsin B (metabolism)
• Colorectal Neoplasms (drug therapy)
• Delayed-Action Preparations (adverse effects, chemistry, pharmacology)
• Doxorubicin (adverse effects, chemistry, pharmacology)
• Drug Carriers
• Female
• Mice
• Mice, Inbred BALB C
• Molecular Structure
• Oligopeptides (chemistry, metabolism)
• Polyethylene Glycols (chemistry)
• Polymers (adverse effects, chemistry, metabolism, pharmacology)