Biodegradable multiblock polymers based on N-(2-hydroxypropyl)methacrylamide designed as drug carriers for tumor-targeted delivery

0461622 - ÚMCH 2017 RIV DE eng J - Článek v odborném periodiku
Mužíková, Gabriela - Pola, Robert - Laga, Richard - Pechar, Michal
Biodegradable multiblock polymers based on N-(2-hydroxypropyl)methacrylamide designed as drug carriers for tumor-targeted delivery.
Macromolecular Chemistry and Physics. Roč. 217, č. 15 (2016), s. 1690-1703. ISSN 1022-1352. E-ISSN 1521-3935
Grant CEP: GA ČR(CZ) GA14-12742S; GA ČR(CZ) GA16-17207S; GA MŠMT(CZ) LO1507; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:61389013
Klíčová slova: biodegradable polymers * click chemistry * drug delivery systems
Kód oboru RIV: CD - Makromolekulární chemie
Impakt faktor: 2.500, rok: 2016

Biodegradable multiblock (co)polymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) for drug delivery applications are prepared by azide–alkyne polycycloaddition of end-functionalized precursors synthesized by reversible addition–fragmentation chain transfer polymerization. Copper-catalyzed polyaddition of the heterotelechelic polymer precursors containing azide and alkyne groups provides (A)x-type multiblock (co)polymers. For the first time, thermally degradable multiblock polymers of (AB)x-type are prepared via polyaddition of homotelechelic polymer diazides with azo-compounds containing two alkyne groups. A novel type of HPMA-based multiblock (co)polymers undergoing the pH-dependent hydrolysis is reported. The (co)polymers containing the Asp-Pro-Lys sequence are relatively stable in an aqueous buffer at physiological pH 7.4; however, they undergo rapid hydrolysis at pH 5.0 corresponding to the pH in lysosomes. The multiblock polymer containing the Gly-Phe-Leu-Lys linkage is degraded in the presence of the lysosomal protease cathepsin B. Thermal degradation of the (AB)x-type multiblock polymers proceeds even at 37 °C, yielding a mixture of polymer degradation products with molecular weights below the renal threshold.
Trvalý link: http://hdl.handle.net/11104/0261226