title: Amphiphilic dendritic derivatives as nanocarriers for the targeted delivery of antimalarial drugs.
abstract: It can be foreseen that in a future scenario of malaria eradication, a varied armamentarium will be required, including strategies for the targeted administration of antimalarial compounds. The development of nanovectors capable of encapsulating drugs and of delivering them to Plasmodium-infected cells with high specificity and efficacy and at an affordable cost is of particular interest. With this objective, dendritic derivatives based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) and Pluronic(®) polymers have been herein explored. Four different dendritic derivatives have been tested for their capacity to encapsulate the antimalarial drugs chloroquine (CQ) and primaquine (PQ), their specific targeting to Plasmodium-infected red blood cells (pRBCs), and their antimalarial activity in vitro against the human pathogen Plasmodium falciparum and in vivo against the rodent malaria species Plasmodium yoelii. The results obtained have allowed the identification of two dendritic derivatives exhibiting specific targeting to pRBCs vs. non-infected RBCs, which reduce the in vitro IC50 of CQ and PQ by ca. 3- and 4-fold down to 4.0 nm and 1.1 μm, respectively. This work on the application of dendritic derivatives to antimalarial targeted drug delivery opens the way for the use of this new type of chemicals in future malaria eradication programs.
authors.affiliation: Departamento de Química Orgánica-Institute of Nanoscience of Aragon (INA), University of Zaragoza, Pedro Cerbuna 12, ES-50009 Zaragoza, Spain.
authors.forename: Julie
authors.initials: J
authors.lastname: Movellan
authors.affiliation: Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Urbán
authors.affiliation: Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Moles
authors.affiliation: Fundación Agencia Aragonesa para la Investigación y el Desarollo (ARAID), María de Luna 11, 1ª planta, Edificio CEEI Aragón, ES-50018 Zaragoza, Spain; Institute of Nanoscience of Aragon (INA), University of Zaragoza, Mariano Esquillor, Edificio I+D, ES-50018 Zaragoza, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: de la Fuente
authors.affiliation: Instituto de Ciencia de Materiales de Aragón (ICMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, ES-50009 Zaragoza, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Sierra
authors.affiliation: Departamento de Química Orgánica-Institute of Nanoscience of Aragon (INA), University of Zaragoza, Pedro Cerbuna 12, ES-50009 Zaragoza, Spain. Electronic address: joseluis@unizar.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Serrano
authors.affiliation: Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain. Electronic address: xfernandez_busquets@ub.edu.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fernàndez-Busquets
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D011319:Primaquine / Q000494:pharmacology / Q000627:therapeutic use; D012235:Rhodamines / Q000378:metabolism; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D013997:Time Factors
chemical_list: D000962:Antimalarials; D050091:Dendrimers; D004337:Drug Carriers; D012235:Rhodamines; D013501:Surface-Active Agents; D002738:Chloroquine; C029773:rhodamine B; D011319:Primaquine
keywords: Antimalarial targeted drug delivery; Dendrimers; Malaria; Nanomedicine; Plasmodium; Polymeric nanoparticles