Biodegradable star HPMA polymer-drug conjugates: biodegradability, distribution and anti-tumor efficacy

0363631 - ÚMCH 2012 RIV NL eng J - Journal Article
Etrych, Tomáš - Kovář, Lubomír - Strohalm, Jiří - Chytil, Petr - Říhová, Blanka - Ulbrich, Karel
Biodegradable star HPMA polymer-drug conjugates: biodegradability, distribution and anti-tumor efficacy.
Journal of Controlled Release. Roč. 154, č. 3 (2011), s. 241-248. ISSN 0168-3659. E-ISSN 1873-4995
R&D Projects: GA AV ČR IAA400500806; GA AV ČR IAAX00500803; GA ČR GAP301/11/0325
Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510
Keywords : star polymer * HPMA copolymers * drug release
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 5.732, year: 2011

New biodegradable star polymer–doxorubicin conjugates designed for passive tumor targeting were investigated, and their synthesis, physico-chemical characterization, drug release, biodegradation, biodistribution and in vivo anti-tumor efficacy are described. In the conjugates, the core formed by poly(amidoamine) (PAMAM) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing doxorubicin (Dox) attached by hydrazone bonds, which enabled intracellular pH-controlled drug release. The described synthesis facilitated the preparation of biodegradable polymer conjugates in a broad range of molecular weights (200–1000 g/mol) while still maintaining low polydispersity (~ 1.7). The polymer grafts were attached to the dendrimers through either stable amide bonds or enzymatically or reductively degradable spacers, which enabled intracellular degradation of the high-molecular-weight polymer carrier to excretable products.
Permanent Link: http://hdl.handle.net/11104/0199377