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HPMA copolymer-doxorubicin conjugates: the effects of molecular weight and architecture on biodistribution and in vivo activity
- 1.0383776 - ÚMCH 2013 RIV NL eng J - Journal Article
Etrych, Tomáš - Šubr, Vladimír - Strohalm, Jiří - Šírová, Milada - Říhová, Blanka - Ulbrich, Karel
HPMA copolymer-doxorubicin conjugates: the effects of molecular weight and architecture on biodistribution and in vivo activity.
Journal of Controlled Release. Roč. 164, č. 3 (2012), s. 346-354. ISSN 0168-3659. E-ISSN 1873-4995.
[European Symposium on Controlled Drug Delivery /12./. Egmond aan Zee, 04.04.2012-06.04.2012]
R&D Projects: GA AV ČR IAAX00500803; GA ČR GAP301/11/0325
Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510
Institutional support: RVO:61389013 ; RVO:61388971
Keywords : drug delivery * tumour accumulation * body distribution
Subject RIV: CD - Macromolecular Chemistry; EC - Immunology (MBU-M)
Impact factor: 7.633, year: 2012
The molecular weight and molecular architecture of soluble polymer drug carriers significantly influence the biodistribution and anti-tumour activities of their doxorubicin (DOX) conjugates in tumour-bearing mice. Biodistribution of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-DOX conjugates of linear and star architectures were compared in EL4 T-cell lymphoma-bearing mice. Biodistribution, including tumour accumulation, and anti-tumour activity of the conjugates strongly depended on conjugate molecular weight (MW), polydispersity, hydrodynamic radius (Rh) and molecular architecture. With increasing MW, renal clearance decreased, and the conjugates displayed extended blood circulation and enhanced tumour accumulation. The linear conjugates with flexible polymer chains were eliminated by kidney clearance more quickly than the highly branched star conjugates with comparable MWs. Interestingly, the data suggested different mechanisms of renal filtration for star and linear conjugates.
Permanent Link: http://hdl.handle.net/11104/0216118
Number of the records: 1