HPMA copolymer-doxorubicin conjugates: the effects of molecular weight and architecture on biodistribution and in vivo activity

0383776 - ÚMCH 2013 RIV NL eng J - Článek v odborném periodiku
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]
Grant CEP: GA AV ČR IAAX00500803; GA ČR GAP301/11/0325
Výzkumný záměr: CEZ:AV0Z40500505; CEZ:AV0Z50200510
Institucionální podpora: RVO:61389013 ; RVO:61388971
Klíčová slova: drug delivery * tumour accumulation * body distribution
Kód oboru RIV: CD - Makromolekulární chemie; EC - Imunologie (MBU-M)
Impakt faktor: 7.633, rok: 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.
Trvalý link: http://hdl.handle.net/11104/0216118