Water-soluble polymer-drug conjugates for combination chemotherapy against visceral leishmaniasis

Bioorg Med Chem. 2010 Apr 1;18(7):2559-65. doi: 10.1016/j.bmc.2010.02.043. Epub 2010 Mar 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemistry*
  • Antiprotozoal Agents / therapeutic use*
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Leishmania donovani / drug effects
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / parasitology
  • Liver / parasitology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / parasitology
  • Mesocricetus
  • Methacrylates
  • Mice
  • Mice, Inbred BALB C
  • Polymers
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Water

Substances

  • Antiprotozoal Agents
  • Methacrylates
  • Polymers
  • Water
  • hydroxypropyl methacrylate