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The structure of polymer carriers controls the efficacy of the experimental combination treatment of tumors with HPMA copolymer conjugates carrying doxorubicin and docetaxel
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SYSNO ASEP 0473875 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The structure of polymer carriers controls the efficacy of the experimental combination treatment of tumors with HPMA copolymer conjugates carrying doxorubicin and docetaxel Author(s) Šírová, Milada (MBU-M) RID, ORCID
Strohalm, Jiří (UMCH-V)
Chytil, Petr (UMCH-V) RID, ORCID
Lidický, Ondřej (UMCH-V) RID
Tomala, Jakub (MBU-M) RID, ORCID
Říhová, Blanka (MBU-M) RID
Etrych, Tomáš (UMCH-V) RID, ORCIDSource Title Journal of Controlled Release. - : Elsevier - ISSN 0168-3659
Roč. 246, JAN 28 (2017), s. 1-11Number of pages 12 s. Language eng - English Country NL - Netherlands Keywords Drug delivery ; HPMA ; Doxorubicin Subject RIV EC - Immunology OECD category Immunology Subject RIV - cooperation Institute of Macromolecular Chemistry - Macromolecular Chemistry R&D Projects GA14-12742S GA ČR - Czech Science Foundation (CSF) GA15-02986S GA ČR - Czech Science Foundation (CSF) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) NV16-28600A GA MZd - Ministry of Health (MZ) GAP301/12/1254 GA ČR - Czech Science Foundation (CSF) Institutional support MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013 UT WOS 000396475500001 EID SCOPUS 85003806562 DOI 10.1016/j.jconrel.2016.12.004 Annotation he tumor-specific targeting of cancerostatics using polymer drug carriers represents a potential strategy to achieve an effective treatment with reduced side toxicity. Synthetic water-soluble copolymers based on N-(2-hydroxypropyl) methacrylamide (HPMA) are carriers with tunable architecture and drug loading, tumor-specific accumulation of the drug, and its controlled release. We describe a combination treatment of murine EL4 T cell lymphoma with HPMA-based star conjugates (M-w 250,000 g mol(-1)) of doxorubicin (Dox) or docetaxel (Dtx) designed for enhanced tumor accumulation and combination therapy. Although the combination of linear conjugates (M-w = 28,000 g mol(-1)) containing Dox or Dtx resulted in an additive effect in the treatment of the lymphoma, the opposite was observed in the combination of two star conjugates with Dox or Dtx, as the star Dtx conjugate decreased the treatment efficacy of the star Dox conjugate. The Dtx conjugate alone was virtually ineffective in the reduction of tumor growth or survival time extension, thus, a curative effect could be solely attributed to the Dox-containing conjugate. When Dtx was delivered to the tumor on the same polymer carrier as Dox, the efficacy of the Dox-induced treatment was reduced to a lesser extent. No reduction was found when Dtx was delivered by a linear polymer or applied as a free drug. The phenomenon was strictly related to the enhanced permeability and retention (EPR) effect, as it was not observed in BCL1 leukemia, a model without EPR. The diminished treatment outcome in the combination therapy with the two star conjugates was underlined by the significantly decreased accumulation of Dox in the tumor. The use of the drug-free polymer carrier instead of the Dtx-containing star conjugate did not reduce the treatment efficacy of the Dox conjugate. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2018
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