title: Poly(amidoamine) conjugates containing doxorubicin bound via an acid-sensitive linker.
abstract: 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.
authors.affiliation: Centre for Polymer Therapeutics, Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff, UK. n.lavignac@kent.ac.uk
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lavignac
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Nicholls
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferruti
authors.forename: Ruth
authors.initials: R
authors.lastname: Duncan
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D002103:Cadaverine / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011108:Polymers / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin; C008542:monodansylcadaverine; D002103:Cadaverine