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

The synthesis of a novel water-soluble polymer drug carrier system based on biodegradable poly(ethylene glycol) block copolymer is described in this p aper. The copolymer consisting of PEG blocks of molecular weight 2000 Linke d by means of an oligopeptide with amino end groups was prepared by interfa cial polycondensation of the diamine and PEG bis(succinimidyl carbonate). T he structure of the oligopeptide diamine consisting of glutamic acid and ly sine residues was designed as a substrate for cathepsin B, a lysosomal enzy me, which was assumed to be one of the enzymes responsible for the degradat ion of the polymer carrier in vivo. Each of the oligopeptide blocks incorpo rated in the carrier contained three carboxylic groups of which some were u sed for attachment of an anti-cancer drug, doxorubicin (Dox), via a tetrape ptide spacer Gly-Phe-Leu-Gly. This tetrapeptide spacer is susceptible to en zymatic hydrolysis. In vitro release of Dox and the degradation of the poly mer chain by cathepsin B as well as preliminary evaluation of in vivo anti- cancer activity of the conjugate are also demonstrated.