Polyamidoamine nanoparticles for the oral administration of antimalarial drugs

Elisabet Martí Coma-Cros, Arnau Biosca, Joana Marques, Laura Carol, Patricia Urbán, Diana Berenguer, Maria Cristina Riera, Michael Delves, Robert E. Sinden, Juan José Valle-Delgado, Lefteris Spanos, Inga Siden-Kiamos, Paula Pérez, Krijn Paaijmans, Matthias Rottmann, Amedea Manfredi, Paolo Ferruti, Elisabetta Ranucci, Xavier Fernàndez-Busquets*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)
121 Downloads (Pure)

Abstract

Current strategies for the mass administration of antimalarial drugs demand oral formulations to target the asexual Plasmodium stages in the peripheral bloodstream, whereas recommendations for future interventions stress the importance of also targeting the transmission stages of the parasite as it passes between humans and mosquitoes. Orally administered polyamidoamine (PAA) nanoparticles conjugated to chloroquine reached the blood circulation and cured Plasmodium yoelii-infected mice, slightly improving the activity of the free drug and inducing in the animals immunity against malaria. Liquid chromatography with tandem mass spectrometry analysis of affinity chromatography-purified PAA ligands suggested a high adhesiveness of PAAs to Plasmodium falciparum proteins, which might be the mechanism responsible for the preferential binding of PAAs to Plasmodium-infected erythrocytes vs. non-infected red blood cells. The weak antimalarial activity of some PAAs was found to operate through inhibition of parasite invasion, whereas the observed polymer intake by macrophages indicated a potential of PAAs for the treatment of certain coinfections such as Plasmodium and Leishmania. When fluorescein-labeled PAAs were fed to females of the malaria mosquito vectors Anopheles atroparvus and Anopheles gambiae, persistent fluorescence was observed in the midgut and in other insect’s tissues. These results present PAAs as a versatile platform for the encapsulation of orally administered antimalarial drugs and for direct administration of antimalarials to mosquitoes, targeting mosquito stages of Plasmodium.

Original languageEnglish
Article number225
JournalPHARMACEUTICS
Volume10
Issue number4
DOIs
Publication statusPublished - 1 Dec 2018
MoE publication typeA1 Journal article-refereed

Keywords

  • Anopheles
  • Antimalarial drugs
  • Malaria
  • Mosquitoes
  • Nanomedicine
  • Nanotechnology
  • Plasmodium
  • Polyamidoamines
  • Polymers
  • Targeted drug delivery

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