Journal
MOLECULAR PHARMACEUTICS
Volume 7, Issue 4, Pages 1027-1040Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp100121g
Keywords
HPMA; branched polymers; EL4 T cell lymphoma; calreticulin; nu/nu mice; acute toxicity; retransplantation; doxorubicin; anticancer immunity
Funding
- Grant Agency of the Academy of Sciences of the Czech Republic [IAAX00500803, IAA400500806]
- Ministry of Education, Youth and Sports of the Czech Republic [1M0505]
- Institutional Research Concept [AV 0Z 50200510]
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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 DOXHYD, 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.
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