Interaction of N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates with human liver microsomal cytochromes P450: comparison with free doxorubicin

0366452 - ÚMCH 2012 RIV US eng J - Journal Article
Mašek, V. - Anzenbacherová, E. - Etrych, Tomáš - Strohalm, Jiří - Ulbrich, Karel - Anzenbacher, P.
Interaction of N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates with human liver microsomal cytochromes P450: comparison with free doxorubicin.
Drug Metabolism and Disposition. Roč. 39, č. 9 (2011), s. 1704-1710. ISSN 0090-9556. E-ISSN 1521-009X
R&D Projects: GA AV ČR KAN200200651
Institutional research plan: CEZ:AV0Z40500505
Keywords : targeted drug delivery * nanomedicine * supramolecular chemistry
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 3.733, year: 2011

Interaction of nine forms of human hepatic cytochromes P450 (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) with two N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based doxorubicin (DOX) conjugates designed for passive tumor targeting was studied using pooled human microsomes. The compounds used in this study were two high-molecular-weight HPMA copolymers bearing doxorubicin attached to the polymeric carrier by 1) hydrazone bond enabling intracellular pH-controlled drug release or 2) amide bond through enzymatically cleavable tetrapeptide GlyPheLeuGly spacer. The extent of inhibition of enzymatic activities of the cytochrome P450 forms studied was negligible with the exception of CYP2B6 and was apparently caused by DOX as no inhibition was observed with polymers alone, and the extent of inhibition by the complex corresponded to this of the free DOX at the same concentration.
Permanent Link: http://hdl.handle.net/11104/0201441