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dc.contributor.authorUnciti-Broceta, Juan Diego
dc.contributor.authorArias Mediano, José Luis 
dc.contributor.authorMaceira, José
dc.contributor.authorSoriano Rodríguez, Miguel
dc.contributor.authorOrtiz-González, Matilde
dc.contributor.authorHernández Quero, José 
dc.contributor.authorMuñoz Torres, Manuel Eduardo 
dc.contributor.authorKoning, Harry P. de
dc.contributor.authorMagez, Stefan
dc.contributor.authorGarcía-Salcedo, José Antonio
dc.date.accessioned2015-09-02T08:55:55Z
dc.date.available2015-09-02T08:55:55Z
dc.date.issued2015
dc.identifier.citationUnciti-Broceta, J.D.; et al. Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis. Plos Pathogens, 11(6): e1004942 (2015). [http://hdl.handle.net/10481/37222]es_ES
dc.identifier.issn1553-7366
dc.identifier.issn1553-7374
dc.identifier.urihttp://hdl.handle.net/10481/37222
dc.description.abstractAfrican trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.es_ES
dc.description.sponsorshipJAGS was funded by the European Union, grant FP7-HEALTH-2007-B-2.3.4-1.223048, NANOTRYP and Ministerio de Economía y Competitividad, Spain Plan Nacional de Investigación grant SAF2011- 30528. JLA was funded by Instituto de Salud Carlos III, Spain, grant FIS. 11/02571. HPdK was supported by a grant from the Medical Research Council (84733).es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS)es_ES
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/223048es_ES
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Licensees_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es_ES
dc.subjectNanoparticleses_ES
dc.subjectMouse modelses_ES
dc.subjectBlood es_ES
dc.subjectParasitic diseases es_ES
dc.subjectTrypanosoma brucei gambiensees_ES
dc.subjectDrug therapyes_ES
dc.subjectPolymerase chain reactiones_ES
dc.subjectDrug deliveryes_ES
dc.titleSpecific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasises_ES
dc.typejournal articlees_ES
dc.rights.accessRightsopen accesses_ES
dc.identifier.doi10.1371/journal.ppat.1004942


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