Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2018 Nov 15

PMID 30423797

Citations 7

Authors

Elisabet Marti Coma-Cros

Arnau Biosca

Joana Marques

Laura Carol

Patricia Urban

Diana Berenguer

Maria Cristina Riera

Michael Delves

Robert E Sinden

Juan Jose Valle-Delgado

Lefteris Spanos

Inga Siden-Kiamos

Paula Perez

Krijn Paaijmans

Matthias Rottmann

Amedea Manfredi

Paolo Ferruti

Elisabetta Ranucci

Xavier Fernandez-Busquets

Affiliations

Soon will be listed here.

Abstract

Current strategies for the mass administration of antimalarial drugs demand oral formulations to target the asexual 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 -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 proteins, which might be the mechanism responsible for the preferential binding of PAAs to -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 and . When fluorescein-labeled PAAs were fed to females of the malaria mosquito vectors and , 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 .

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