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High-molecular weight HPMA copolymer–adriamycin conjugates

1999; Elsevier BV; Volume: 60; Issue: 2-3 Linguagem: Inglês

10.1016/s0168-3659(99)00087-5

1873-4995

M Dvořák, Pavla Kopečková, Jindřich Kopeček,

Luminescence and Fluorescent Materials

High-molecular weight (branched) water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing lysosomally degradable oligopeptide crosslinks were synthesized by radical copolymerization of HPMA and newly designed crosslinking agents, N(2), N(5)-bis(N-methacryloylglycylphenylalanylleucylglycyl)ornithine s with different modification of the carboxy group. The length of the primary chain was controlled by the addition of a chain transfer agent, 3-mercaptopropionic acid. A polymerizable derivative of the anticancer drug adriamycin (ADR), N-methacryloylglycylphenylalanylleucylglycyl adriamycin, was added to some polymerization mixtures. This resulted in high-molecular weight, branched, water-soluble HPMA copolymers containing oligopeptide sequences in the crosslinks as well as in side-chains terminated in ADR. The degradability of the crosslinks as well as the release of ADR by lysosomal enzymes isolated from rat liver were investigated.