Poly(amidoamine) conjugates containing doxorubicin bound via an acid-sensitive linker.

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.