Synergistic effect of HPMA copolymer-bound doxorubicin and dexamethasone in vivo on mouse lymphomas

0359969 - ÚMCH 2012 RIV GB eng J - Journal Article
Kostková, Hana - Etrych, Tomáš - Říhová, Blanka - Ulbrich, Karel
Synergistic effect of HPMA copolymer-bound doxorubicin and dexamethasone in vivo on mouse lymphomas.
Journal of Bioactive and Compatible Polymers. Roč. 26, č. 3 (2011), s. 270-286. ISSN 0883-9115. E-ISSN 1530-8030
R&D Projects: GA AV ČR IAAX00500803; GA AV ČR IAA400500806; GA MŠMT 1M0505
Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510
Keywords : HPMA copolymer * doxorubicin * dexamethasone
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 2.953, year: 2011

N-(2-Hydroxypropyl)methacrylamide copolymer—drug conjugates bearing the antiinflammatory and anti-proliferative drug dexamethasone (DEX) and the anti-cancer drug doxorubicin (DOX) bound to either the polymer carrier separately or in combination, were synthesized. Both the in vitro and in vivo anti-cancer activity on mouse B-cell (38C13) and T-cell (EL4) lymphoma was studied. The conjugates were fairly stable in model buffers at pH 7.4, simulating blood pH, and the drug was released by chemical hydrolysis at pH values based on the endosomal and lysosomal environments in the target cells (pH 5—6).Contrary to the treatment with either single drug conjugate, where no significant long-term survival was observed, a synergistic effect of the two drugs was manifested in vivo. Treatment of mice bearing B-cell lymphoma 38C13 formulated as a mixture of both single drug-containing conjugates or a as a conjugate with both drugs in combination gave long-term survivors.
Permanent Link: http://hdl.handle.net/11104/0006466