Poly(amidoamine) Conjugates Containing Doxorubicin Bound via an Acid-Sensitive Linker

Authors

  • Nathalie Lavignac,

    Corresponding author
    1. Centre for Polymer Therapeutics, Welsh School of Pharmacy, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3XF, UK
    2. School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, ME4 4TB, UK
    • School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, ME4 4TB, UK. Fax: +44 1634 883 927
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  • Johanna L. Nicholls,

    1. Centre for Polymer Therapeutics, Welsh School of Pharmacy, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3XF, UK
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  • Paolo Ferruti,

    1. Dipartimento di Chimica Organica e Industriale and Centro Interdisciplinare Materiali Innovativi Nanostrutturati, Università di Milano, Via Venezian 21, 20133 Milano, Italy
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  • Ruth Duncan

    1. Centre for Polymer Therapeutics, Welsh School of Pharmacy, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3XF, UK
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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 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 (IC50 = 6 µg Dox · mL−1) presented similar toxicity as the parent polymer without Dox, ISA23Dox showed increased toxicity (IC50 = 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.

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