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Poly(amidoamine) Conjugates Containing Doxorubicin Bound via an Acid‐Sensitive Linker
Author(s) -
Lavignac Nathalie,
Nicholls Johanna L.,
Ferruti Paolo,
Duncan Ruth
Publication year - 2009
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.200800163
Subject(s) - amidoamine , poly(amidoamine) , conjugate , linker , chemistry , doxorubicin , cadaverine , polymer , stereochemistry , polymer chemistry , combinatorial chemistry , dendrimer , organic chemistry , enzyme , putrescine , medicine , mathematical analysis , mathematics , surgery , chemotherapy , computer science , operating system
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 µg of DC per mg of polymer and 28 to 35 µg 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 µg Dox · mL −1 ) presented similar toxicity as the parent polymer without Dox, ISA23Dox showed increased toxicity (IC 50 = 10 µg Dox · 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.