Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin

0353988 - ÚMCH 2011 RIV NL eng J - Journal Article
Studenovský, Martin - Ulbrich, Karel - Ibrahimová, Markéta - Říhová, Blanka
Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin.
European Journal of Pharmaceutical Sciences. Roč. 42, 1-2 (2011), s. 156-163. ISSN 0928-0987. E-ISSN 1879-0720
R&D Projects: GA AV ČR IAAX00500803
Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510
Keywords : polymer conjugates * tumor drug-delivery * pH-controlled release
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 3.212, year: 2011

This paper describes the synthesis and biological evaluation of a conjugate of the highly cytotoxic drug 2-pyrrolinodoxorubicin (p-DOX) with an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA), utilizing the advantageous concept of polymer–drug conjugates. The hydrazone bond between the polymer and drug is susceptible to pH-controlled hydrolysis, enabling prolonged stability in circulation and fast p-DOX release under conditions mimicking the intracellular environment. The in vitro cytostatic activity of free p-DOX was in accordance with literature, whereas its PHPMA conjugate exhibited a 1.3- to 5-fold lower cytotoxicity, depending on the cancer cell line, when compared to the free p-DOX. On mice bearing T-cell EL4 lymphoma, no tumor suppression was observed from the free p-DOX at a subtoxic dose of 0.1 mg/kg, whereas the PHPMA/p-DOX conjugate significantly inhibited the initial tumor growth at approximately equitoxic doses of 0.4 and 0.8 mg p-DOX eq/kg.
Permanent Link: http://hdl.handle.net/11104/0006249