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N‐ (2‐hydroxypropyl)methacrylamide‐based polymer conjugates with pH‐controlled activation of doxorubicin. I. New synthesis, physicochemical characterization and preliminary biological evaluation
Author(s) -
Etrych Tomáš,
Mrkvan Tomáš,
Chytil Petr,
Koňák Čestmír,
Říhová Blanka,
Ulbrich Karel
Publication year - 2008
Publication title -
journal of applied polymer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.575
H-Index - 166
eISSN - 1097-4628
pISSN - 0021-8995
DOI - 10.1002/app.28466
Subject(s) - methacrylamide , conjugate , hydrazide , copolymer , chemistry , doxorubicin , hydrazone , combinatorial chemistry , polymer , polymer chemistry , acrylamide , organic chemistry , chemotherapy , medicine , mathematical analysis , mathematics , surgery
New method of synthesis of water‐soluble polymer‐drug conjugates, exhibiting remarkable anticancer activity in mice models, has been developed. In the conjugates, an anticancer drug doxorubicin (DOX) is attached to a polymer carrier based on N ‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer via a hydrolytically labile hydrazone bond. New methacrylamide‐type comonomers, containing either hydrazide group or hydrazon of DOX, were used for copolymerization with HPMA. In contrast to the synthetic procedure described earlier the new method is simpler, cheaper, and results in a better‐defined conjugate structure. The conjugates are fairly stable in buffer at pH 7.4 (model of blood stream) but release DOX under mild acid conditions modeling the tumor microenvironment. The conjugates showed significant in vivo antitumor activity in treatment of T‐cell lymphoma EL‐4 bearing mice with up to 100% long‐term survivors. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008