Novel star HPMA-based polymer conjugates for passive targeting to solid tumors

0367005 - ÚMCH 2012 RIV GB eng J - Journal Article
Etrych, Tomáš - Strohalm, Jiří - Chytil, Petr - Říhová, Blanka - Ulbrich, Karel
Novel star HPMA-based polymer conjugates for passive targeting to solid tumors.
Journal of Drug Targeting. Roč. 19, č. 10 (2011), s. 874-889. ISSN 1061-186X. E-ISSN 1029-2330
R&D Projects: GA AV ČR IAA400500806; GA AV ČR IAAX00500803; GA ČR GAP301/11/0325
Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510
Keywords : drug delivery * controlled release * HPMA
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 2.696, year: 2011

Novel star polymer-doxorubicin conjugates designed for passive tumor targeting have been developed and their potential for treatment of cancer has been investigated. In the present study the synthesis, physico-chemical characterization, drug release, bio-distribution and preliminary data of in vivo efficacy of the conjugates are described. In the water-soluble conjugates the core of a molecule formed by poly(amido amine) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide copolymers bearing doxorubicin attached by hydrazone bonds enabling intracellular pH-controlled hydrolytic drug release, or by GFLG sequence susceptible to enzymatic degradation. The controlled synthesis utilizing semitelechelic copolymer precursors facilitated preparation of polymer conjugates in a broad range of molecular weights. The star polymer-Dox conjugates showed significantly higher anti-tumor activity in vivo than Dox HCl or its linear or graft polymer conjugates.
Permanent Link: http://hdl.handle.net/11104/0201807