Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

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.

Promising nanomaterials in the fight against malaria

“…In addition, these structures together with a cationic poly(amidoamino acid) containing L-arginine units, ARGO7, were thoroughly studied by the same group for the oral administration of CQ. 96 Further traceability studies of the empty polyamidoamines labeled with fluorescein and orally administered to female Anopheles gambiae mosquitoes postulated these polymeric platforms as good NCs to directly target Plasmodium in the mosquito vector. 97 Biodegradable synthetic polymers such as poly(D,L-lactic-coglycolic acid) (PLGA), polyalkylcyanoacrylates or poly(D,L-lactic acid) have been broadly used to prepare polymeric NPs.…”

“…Chemical structures of AGMA1, ISA23, ISA1 and ARGO7 95,96. Journal of Materials Chemistry B Review Open Access Article.…”

Polyamidoamines: Versatile Bioactive Polymers with Potential for Biotechnological Applications

“…Several PAA/chloroquine formulations obtained with ISA23, ISA1, AGMA and ARGO7 cured Plasmodium yoelii-infected mice, improved the activity of the free drug and induced in the animals immunity against malaria [98]. PAA adhesiveness to Plasmodium falciparum proteins was ascribed as responsible for the preferential binding of PAAs to Plasmodium-infected erythrocytes with respect to noninfected red blood cells.…”

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“…[24][25][26][27] As the first commercialized dendrimer family, poly(amidoamine) (PAMAM) dendrimers with tens of terminal functional groups have been widely used as macroinitiators to synthesize dendritic polymers. [28][29][30][31] For example, the biocompatible and biodegradable PAMAM-based poly(γ-benzyl-L-glutamate) (PBLG) was synthesized from directly initiating the ring-opening polymerization of γ-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) monomers by amino-terminated PAMAM. Recently reports show that aryl group-containing drugs like paclitaxel are efficiently loaded by nanoparticles fabricated from aromatic groups-containing polymers via noncovalent pi-pi stacking interaction, with significantly improved stability in vivo.…”