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Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain
Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, ES-08028 Barcelona, Spain
Laboratori de Parasitologia, Departament de Microbiologia i Parasitologia Sanitàries, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, ES-08028 Barcelona, Spain
Department of Life Sciences, Imperial College, South Kensington, London SW7 2AZ, UK
Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, P.O. Box 16300, FI-00076 Aalto, Finland
Institute of Molecular Biology and Biotechnology, FORTH, N. Plastira 100, 700 13 Heraklion, Greece
Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4051 Basel, Switzerland
Universität Basel, Petersplatz 1, CH-4003 Basel, Switzerland
Dipartimento di Chimica, Università degli Studi di Milano, via Golgi 19, IT-20133 Milano, Italy
Author to whom correspondence should be addressed.
Pharmaceutics 2018, 10(4), 225;
Received: 19 October 2018 / Revised: 5 November 2018 / Accepted: 6 November 2018 / Published: 10 November 2018
(This article belongs to the Special Issue From Drug Carriers to Vaccine Adjuvants in Malaria)
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. View Full-Text
Keywords: Anopheles; antimalarial drugs; malaria; mosquitoes; nanomedicine; nanotechnology; Plasmodium; polymers; polyamidoamines; targeted drug delivery Anopheles; antimalarial drugs; malaria; mosquitoes; nanomedicine; nanotechnology; Plasmodium; polymers; polyamidoamines; targeted drug delivery
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Martí Coma-Cros, E.; Biosca, A.; Marques, J.; Carol, L.; Urbán, P.; Berenguer, D.; Riera, M.C.; Delves, M.; Sinden, R.E.; Valle-Delgado, J.J.; Spanos, L.; Siden-Kiamos, I.; Pérez, P.; Paaijmans, K.; Rottmann, M.; Manfredi, A.; Ferruti, P.; Ranucci, E.; Fernàndez-Busquets, X. Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs. Pharmaceutics 2018, 10, 225.

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