High-molecular weight HPMA copolymer-adriamycin conjugates.
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.
Dvorák
M
M
Departments of Pharmaceutics and Pharmaceutical Chemistry/CCCD, and of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
Kopecková
P
P
Kopecek
J
J
D015097:3-Mercaptopropionic Acid / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D001673:Biodegradation, Environmental; D003432:Cross-Linking Reagents / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry*; D008099:Liver / Q000502:physiology*; D008247:Lysosomes / Q000502:physiology*; D008689:Methacrylates / Q000737:chemistry*; D009952:Ornithine / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D008689:Methacrylates; D011108:Polymers; D004317:Doxorubicin; D015097:3-Mercaptopropionic Acid; D009952:Ornithine; C032802:hydroxypropyl methacrylate