Lavignac Nathalie, Nicholls Johanna L, Ferruti Paolo, Duncan Ruth
Centre for Polymer Therapeutics, Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff, UK.
Macromol Biosci. 2009 May 13;9(5):480-7. doi: 10.1002/mabi.200800163.
Poly(amidoamine)s with amino pendant groups were prepared by hydrogen-transfer polyaddition of primary and secondary amines to bis-acrylamines. Dansyl cadaverine (DC) doxorubicin (Dox) were bound to the polymers via a cis-aconityl spacer to give conjugates containing 3 microg of DC per mg of polymer and 28 to 35 microg of Dox per mg of polymer. Release of DC and Dox at physiological and acidic pH varied from 0 to 35% over 48 h and was pH dependent. Although the ISA1Dox conjugate (IC(50) = 6 microg Dox x mL(-1)) presented similar toxicity as the parent polymer without Dox, ISA23Dox showed increased toxicity (IC(50) = 10 microg Dox x mL(-1)). These results suggest that ISA23Dox is able to release biologically active Dox in vitro and that this conjugate might be suitable for further development.
通过伯胺和仲胺与双丙烯酰胺的氢转移聚加成反应制备了带有氨基侧基的聚（酰胺胺）。丹磺酰尸胺（DC）和阿霉素（Dox）通过顺乌头酰间隔基与聚合物结合，得到每毫克聚合物含有3微克DC和每毫克聚合物含有28至35微克Dox的缀合物。在生理和酸性pH条件下，DC和Dox在48小时内的释放量从0到35%不等，且依赖于pH值。尽管ISA1Dox缀合物（IC50 = 6微克Dox×mL-1）表现出与不含Dox的母体聚合物相似的毒性，但ISA23Dox显示出更高的毒性（IC50 = 10微克Dox×mL-1）。这些结果表明，ISA23Dox能够在体外释放具有生物活性的Dox，并且这种缀合物可能适合进一步开发。
