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Review
. 2016 Sep 28:7:351.
doi: 10.3389/fphar.2016.00351. eCollection 2016.

New Approaches to Overcome Transport Related Drug Resistance in Trypanosomatid Parasites

Jose A Garcia-Salcedo  1 , Juan D Unciti-Broceta  2 , Javier Valverde-Pozo  1 , Miguel Soriano  3
Affiliations
Review

New Approaches to Overcome Transport Related Drug Resistance in Trypanosomatid Parasites

Jose A Garcia-Salcedo et al. Front Pharmacol. .

Abstract

Leishmania and Trypanosoma are members of the Trypanosomatidae family that cause severe human infections such as leishmaniasis, Chagas disease, and sleeping sickness affecting millions of people worldwide. Despite efforts to eradicate them, migrations are expanding these infections to developing countries. There are no vaccines available and current treatments depend only on chemotherapy. Drug resistance is a major obstacle for the treatment of these diseases given that existing drugs are old and limited, with some having severe side effects. Most resistance mechanisms developed by these parasites are related with a decreased uptake or increased efflux of the drug due to mutations or altered expression of membrane transporters. Different new approaches have been elaborated that can overcome these mechanisms of resistance including the use of inhibitors of efflux pumps and drug carriers for both active and passive targeting. Here we review new formulations that have been successfully applied to circumvent resistance related to drug transporters, opening alternative ways to solve drug resistance in protozoan parasitic diseases.

Keywords: drug resistance; drug transport; efflux pumps; nanocarriers; surface transporter; trypanosomatid parasites.

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Figures

FIGURE 1
FIGURE 1
Common mechanisms for drug resistance.
FIGURE 2
FIGURE 2
Drug transporters in T. brucei.
FIGURE 3
FIGURE 3
Drug transporters in Leishmania. K, kinetoplast; N, nucleus.
FIGURE 4
FIGURE 4
Strategy to overcome drug resistance associated to mutations in surface transporter in T. brucei based on nanobody-coated pentamidine loaded nanoparticle.
See this image and copyright information in PMC

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References

    1. Allahverdiyev A. M., Abamor E. S., Bagirova M., Rafailovich M. (2011). Antimicrobial effects of TiO(2) and Ag(2)O nanoparticles against drug-resistant bacteria and leishmania parasites. Future Microbiol. 6 933–940. 10.2217/FMB.11.78 - DOI - PubMed
    1. Alsford S., Eckert S., Baker N., Glover L., Sanchez-Flores A., Leung K. F., et al. (2012). High-throughput decoding of antitrypanosomal drug efficacy and resistance. Nature 482 232–236. 10.1038/nature10771 - DOI - PMC - PubMed
    1. Alzate J. F., Arias A., Mollinedo F., Rico E., de la Iglesia-Vicente J., Jimenez-Ruiz A. (2008). Edelfosine induces an apoptotic process in Leishmania infantum that is regulated by the ectopic expression of Bcl-XL and Hrk. Antimicrob. Agents Chemother. 52 3779–3782. 10.1128/AAC.01665-07 - DOI - PMC - PubMed
    1. Antimisiaris S. G., Ioannou P. V., Loiseau P. M. (2003). In-vitro antileishmanial and trypanocidal activities of arsonoliposomes and preliminary in-vivo distribution in BALB/c mice. J. Pharm. Pharmacol. 55 647–652. 10.1211/002235703765344559 - DOI - PubMed
    1. Arias J. L., Unciti-Broceta J. D., Maceira J., Del Castillo T., Hernandez-Quero J., Magez S., et al. (2015). Nanobody conjugated PLGA nanoparticles for active targeting of African trypanosomiasis. J. Control. Release 197 190–198. 10.1016/j.jconrel.2014.11.002 - DOI - PubMed