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Water-soluble polymer–drug conjugates for combination chemotherapy against visceral leishmaniasis
Authors:Salvatore Nicoletti  Karin Seifert  Ian H Gilbert
Institution:1. Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee DD1 5EH, UK;2. London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
Abstract:There is a need for new safe, effective and short-course treatments for leishmaniasis; one strategy is to use combination chemotherapy. Polymer–drug conjugates have shown promise for the delivery of anti-leishmanial agents such as amphotericin B. In this paper, we report on the preparation and biological evaluation of polymer–drug conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA), amphotericin B and alendronic acid. The combinatorial polymer–drug conjugates were effective anti-leishmanial agents in vitro and in vivo, but offered no advantage over the single poly(HPMA)–amphotericin B conjugates.
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