Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic.
Mol Pharm. 2010 Aug 2;7(4):1027-40. doi: 10.1021/mp100121g.
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.
基于 N-(2-羟丙基)甲基丙烯酰胺共聚物 (PHPMA) 的聚合物缀合物（通过酰胺和腙键结合阿霉素的聚合物缀合物）的细胞抑制作用与通过酰胺或腙键结合药物的单缀合物的细胞抑制作用进行了比较。一组混合缀合物由两种共单体组成，其中一种共单体通过间隔基与丙烯酰基结合的阿霉素（DOX(AM)) 或腙（DOX(HYD)) 通过与 HPMA 共聚形成键。第二组混合缀合物由两种不同的互连 HPMA 共聚物组成，一种含有 DOX(AM)，另一种含有 DOX(HYD)，形成高分子量支化结构。第三种混合聚合物系统是单缀合的 DOX(AM)-PHPMA 和 DOX(HYD)-PHPMA 的简单混合物。在用单缀合物给药后，同时使用所有混合形式的多柔比星聚合物衍生物可显著提高抗肿瘤疗效，这表明存在协同作用，可用于设计新的含多柔比星的治疗系统。
