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Polyamidoamine nanoparticles for the oral administration of antimalarial drugs

Martí Coma-Cros, Elisabet and Biosca, Arnau and Marques, Joana and Carol, Laura and Urbán, Patricia and Berenguer, Diana and Riera, Maria Cristina and Delves, Michael and Sinden, Robert E. and Valle-Delgado, Juan José and Spanos, Lefteris and Siden-Kiamos, Inga and Pérez, Paula and Paaijmans, Krijn and Rottmann, Matthias and Manfredi, Amedea and Ferruti, Paolo and Ranucci, Elisabetta and Fernàndez-Busquets, Xavier. (2018) Polyamidoamine nanoparticles for the oral administration of antimalarial drugs. Pharmaceutics, 10 (4). p. 225.

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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; .
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Rottmann, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:MDPI
ISSN:1999-4923
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:22 Nov 2018 14:32
Deposited On:22 Nov 2018 14:32

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