Synergistic action of doxorubicin bound to the polymeric carrier based on N-(2-hydroxypropyl)methacrylamide copolymers through an amide or hydrazone bond.
The cytostatic effects of polymeric conjugates based on N-(2-hydroxypropyl)methacrylamide copolymers (PHPMA) and containing doxorubicin bound through amide and hydrazone bonds (mixed conjugates) were compared with the cytostatic effects of monoconjugates containing drug bound through an amide or hydrazone bond. One group of mixed conjugates was formed from two comonomers containing doxorubicin bound to the methacryloyl group through a spacer and an amide (DOX(AM)) or hydrazone (DOX(HYD)) bond via copolymerization with HPMA. A second group of mixed conjugates was formed from two different interconnected HPMA copolymers, one containing DOX(AM) and the other DOX(HYD), forming a high-molecular-weight branched structure. The third mixed polymeric system was a simple mixture of monoconjugates DOX(AM)-PHPMA and DOX(HYD)-PHPMA. Simultaneous treatment with all mixed forms of the polymeric derivatives of doxorubicin significantly increased antitumor efficacy after application of monoconjugates, suggesting a synergizing effect that could be used in designing new doxorubicin-containing therapeutic systems.
Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic. rihova@biomed.cas.cz
B
B
Ríhová
T
T
Etrych
M
M
Sírová
L
L
Kovár
O
O
Hovorka
M
M
Kovár
A
A
Benda
K
K
Ulbrich
D000178:Acrylamides / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D016399:Lymphoma, T-Cell / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
D000178:Acrylamides; D000577:Amides; D000903:Antibiotics, Antineoplastic; D006835:Hydrazones; D011108:Polymers; D004317:Doxorubicin; C032976:N-(2-hydroxypropyl)methacrylamide