Abstract
The synthesis, characterization and results of evaluation of the biological behavior of HPMA copolymer conjugates bearing anti-cancer drugs doxorubicin and mitomycin C are described. Two HPMA copolymer carrier types were synthesized: the linear copolymer and the biodegradable high-molecular-weight diblock copolymer containing a degradable disulfide bond. The polymer-drug conjugates incubated in buffers modeling the intracellular environment released the drugs more rapidly than those incubated in bloodstream conditions. Significant in vitro and in vivo antitumor synergistic activity of the conjugates in the treatment of EL-4 T-cell demonstrates their high potential for solid tumor treatment.
Keywords:
HPMA copolymers; Mitomycin C; combination therapy; doxorubicin; tumor treatment.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acrylamides / chemistry*
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Carcinoma / drug therapy
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Carcinoma / mortality
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Carcinoma / pathology
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Carcinoma, Lewis Lung / drug therapy
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Carcinoma, Lewis Lung / mortality
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Carcinoma, Lewis Lung / pathology
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Cell Line, Tumor
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Cytotoxins / chemistry
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Cytotoxins / pharmacology*
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Disulfides
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Doxorubicin / chemistry
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Doxorubicin / pharmacology*
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Drug Carriers / chemical synthesis*
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Drug Therapy, Combination
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Female
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Kinetics
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Levulinic Acids / chemistry
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Lymphoma, B-Cell / drug therapy
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Lymphoma, B-Cell / mortality
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Lymphoma, B-Cell / pathology
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Lymphoma, T-Cell / drug therapy
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Lymphoma, T-Cell / mortality
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Lymphoma, T-Cell / pathology
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Mammary Glands, Animal / drug effects
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Mammary Glands, Animal / pathology
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Mice
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Mice, Inbred C57BL
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Mitomycin / chemistry
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Mitomycin / pharmacology*
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Neoplasm Transplantation
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Survival Analysis
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Tumor Burden / drug effects
Substances
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Acrylamides
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Antineoplastic Agents
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Cytotoxins
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Disulfides
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Drug Carriers
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Levulinic Acids
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Mitomycin
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Doxorubicin
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N-(2-hydroxypropyl)methacrylamide
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levulinic acid