Journal
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS
Volume 26, Issue 3, Pages 270-286Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0883911511406326
Keywords
HPMA copolymer; doxorubicin; dexamethasone; drug delivery; combination therapy; B-cell lymphoma; T-cell lymphoma
Funding
- Grant Agency of the Academy of Sciences of the Czech Republic [IAAX00500803, IAA400500806]
- MSMT [IM463560802]
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N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymer-drug conjugates bearing the anti-inflammatory 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). As a control, polymer conjugates containing only a single-drug (DOX or DEX) attached to the HPMA copolymer carrier were synthesized and tested. 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.
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