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Solving the challenge of the blood–brain barrier to treat infections caused by Trypanosoma evansi: evaluation of nerolidol-loaded nanospheres in mice

Published online by Cambridge University Press:  23 June 2017

MATHEUS D. BALDISSERA ,
CARINE F. SOUZA ,
ALINE A. BOLIGON ,
THIRSSA H. GRANDO ,
MARIÂNGELA F. DE SÁ ,
ALEKSANDRO S. DA SILVA ,
LENITA M. STEFANI ,
BERNARDO BALDISSEROTTO  and
SILVIA G. MONTEIRO
MATHEUS D. BALDISSERA*
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
CARINE F. SOUZA
Affiliation:
Department of Physiology and Pharmacology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
ALINE A. BOLIGON
Affiliation:
Laboratory of Phytochemistry, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil
THIRSSA H. GRANDO
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
MARIÂNGELA F. DE SÁ
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
ALEKSANDRO S. DA SILVA
Affiliation:
Department of Animal Science, Universidade do Estado de Santa Catarina (UDESC), Chapecó, SC, Brazil
LENITA M. STEFANI
Affiliation:
Department of Animal Science, Universidade do Estado de Santa Catarina (UDESC), Chapecó, SC, Brazil
BERNARDO BALDISSEROTTO
Affiliation:
Department of Physiology and Pharmacology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
SILVIA G. MONTEIRO*
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
*
*Corresponding authors: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. E-mail: matheusd.biomed@yahoo.com.br and sgmonteiro@uol.com.br
*Corresponding authors: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. E-mail: matheusd.biomed@yahoo.com.br and sgmonteiro@uol.com.br
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Summary

Despite significant advances in therapies against Trypanosoma evansi, its effective elimination from the central nervous system (CNS) remains a difficult task. The incapacity of trypanocidal drugs to cross the blood–brain barrier (BBB) after systemic administrations makes the brain the main refuge area for T. evansi. Nanotechnology is showing great potential to improve drug efficacy, such as nerolidol-loaded nanospheres (N-NS). Thus, the aim of this study was to investigate whether the treatment with N-NS was able to cross the BBB and to eliminate T. evansi from the CNS. High-performance liquid chromatography revealed that N-NS can cross the BBB of T. evansi-infected mice, while free nerolidol (F-N) neither the trypanocidal drug diminazene aceturate (D.A.) were not detected in the brain tissue. Polymerase chain reaction revealed that 100% of the animals treated with N-NS were negatives for T. evansi in the brain tissue, while all infected animals treated with F-N or D.A. were positives. Thus, we concluded that nanotechnology improves the therapeutic efficacy of nerolidol, and enables the transport of its active principle through the BBB. In summary, N-NS treatment can eliminate the parasite from the CNS, and possesses potential to treat infected animals.

Keywords

central nervous systemnanotechnologynatural products
Type
Research Article
Information
Parasitology , Volume 144 , Issue 11 , September 2017 , pp. 1543 - 1550
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Copyright
Copyright © Cambridge University Press 2017 

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References

REFERENCES

Abamor, E. S. and Allahverdiyev, A. M. (2016). A nanotechnology based new approach for chemotherapy of cutaneous leishmaniasis: TIO2@AG nanoparticles – Nigella sativa oil combinations. Experimental Parasitology 166, 150–163.CrossRefGoogle ScholarPubMed
Acosta, H., Rondón-Mercado, R., Avilán, L. and Concepción, J. L. (2016). Interaction of Trypanosoma evansi with the plasminogen-plasmin system. Veterinary Parasitology 226, 189–197.CrossRefGoogle ScholarPubMed
Amaral, R. G., Baldissera, M. D., Grando, T. H., Couto, J. C. M., Posser, C. P., Ramos, A. P., Sagrillo, M. R., Vaucher, R. A., Da Silva, A. S., Becker, A. P. and Monteiro, S. G. (2016). Combination of the essential oil constituents α-pinene and β-caryophyllene as a potentiator of trypanocidal action on Trypanosoma evansi . Journal of Applied Biomedicine 14, 265–272.CrossRefGoogle Scholar
Baker, N., de Koning, H. P., Maser, P. and Horn, D. (2013). Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story. Trends in Parasitology 29, 110–118.CrossRefGoogle ScholarPubMed
Baldissera, M. D., Rech, V. C., Da Silva, A. S., Nishihira, V. S. K., Ianiski, F. R., Gressler, L. T., Grando, T. H., Vaucher, R. A., Schwertz, C. I., Mendes, R. E. and Monteiro, S. G. (2015). Relationship between behavioral alterations and activities of adenylate kinase and creatine kinase of rats infected by Trypanosoma evansi . Experimental Parasitology 151–152, 96–102.CrossRefGoogle ScholarPubMed
Baldissera, M. D., Grando, T. H., Souza, C. F., Cossetin, L. F., Sagrillo, M. R., Nascimento, K., da Silva, A. P. T., Dalla Lana, D. F., Da Silva, A. S., Stefani, L. M. and Monteiro, S. G. (2016 a). Nerolidol nanospheres increases its trypanocidal efficacy against Trypanosoma evansi: new approach against diminazene aceturate resistance and toxicity. Experimental Parasitology 166, 144–149.CrossRefGoogle ScholarPubMed
Baldissera, M. D., Gonçalves, R. A., Sagrillo, M. R., Grando, T. H., Ritter, C. S., Grotto, F. S., Brum, G. F., da Luz, S. C. A., Silveira, S. O., Fausto, V. P., Boligon, A. A., Vaucher, R. A., Stefani, L. M., da Silva, A. S., Souza, C. F. and Monteiro, S. G. (2016 b). Effects of treatment with the anti-parasitic drug diminazene aceturate on antioxidant enzymes in rat liver and kidney. Naunyn-Schmiedeberg's Archives of Pharmacology 389, 429–438.CrossRefGoogle ScholarPubMed
Baldissera, M. D., Souza, C. F., Grando, T. H., Moreira, K. L. S., Schafer, A. S., Cossetin, L. F., da Silva, A. P. T., da Veiga, M. L., da Rocha, M. I. U. M., Stefani, L. M., da Silva, A. S. and Monteiro, S. G. (2017). Nerolidol-loaded nanospheres prevent behavioral impairment via ameliorating Na+, K+-ATPase and AChE activities as well as reducing oxidative stress in the brain Trypanosoma evansi-infected mice. Naunyn-Schmiedeberg's Archives of Pharmacology 390, 139–148.Google Scholar
Chau, N. V. V., Chau, L. B., Desquesnes, M., Herder, M., Lan, N. P. H. L., Campbell, J. I., Cuong, N. V., Yimming, B., Chalermwong, P., Jittapalalong, S., Franco, J. R., Tue, N. T., Rabaa, M. A., Carrique-Mas, J., Thanh, T. P. T., Thieu, N. T. V., Berto, A., Hoa, N. T., Hoang, N. V. M., Tu, N. C., Chuyen, N. K., Wills, B., Hien, T. T., Thwaites, G. E., Yacoub, S. and Baker, S. (2016). A clinical and epidemiological investigation of the first reported human infection with the zoonotic parasite Trypanosoma evansi in southeast Asia. Clinical Infectious Diseases. 62, 1002–1008.CrossRefGoogle Scholar
Colpo, C. B., Monteiro, S. G., Stainki, D. R., Colpo, E. T. B. and Henriques, G. B. (2005). Natural infection by Trypanosoma evansi in dogs. Ciência Rural 35, 717–719.CrossRefGoogle Scholar
Da Silva, A. S., Doyle, R. L. and Monteiro, S. G. (2006). Métodos de contenção e confecção de esfregaço sanguíneo para pesquisa de hemoparasitas em ratos e camundongos. Revista da Faculdade de Medicina Veterinária e Zootecnia 3, 83–87.Google Scholar
Da Silva, A. S., Spanevello, R., Stefanello, N., Wolkmer, P., Costa, M. M., Zanette, R. A., Lopes, S. T. A., Santurio, J. M., Schetinger, M. R. C. and Monteiro, S. G. (2010). Influence of Trypanosoma evansi in blood, plasma, and brain cholinesterase of experimentally infected rats. Research in Veterinary Science 88, 281–284.CrossRefGoogle Scholar
De Luca, M. A., Lai, F., Corrias, F., Caboni, P., Bimpisidis, Z., Maccioni, E., Fadda, A. M. and Di Chiari, G. (2015). Lactoferrin-and antitransferrin-modified liposomes for brain targeting of the NK3 receptor agonist senktide: preparation and in vivo evaluation. International Journal of Pharmaceuticals 479, 129–137.CrossRefGoogle Scholar
Fessi, H., Puiseux, J., Devissaguet, N., Ammoury, N. and Benita, S. (1989). Nanocapsule formation by interfacial polymer deposition following solvent displacement. International Journal of Pharmaceutics 55, 1–4.CrossRefGoogle Scholar
Garcia-Garcia, E., Andrieux, K., Gil, S. and Couvreur, P. (2005). Colloidal carriers and blood-brain (BBB) translocation: a way to deliver drugs to the brain? International Journal of Pharmaceutics 298, 274–292.CrossRefGoogle ScholarPubMed
Gruber, J. W., Kittipongpatana, N., Bloxton, I. I. J. D., Marderosian, A. D., Schaefer, F. T. and Gibbs, R. (2004). High-Performance Liquid Chromatography and Thin-Layer Chromatography Assays for Devil's Club (Oplopanax horridus). Journal of Chromatographic Science 42, 196–199.Google Scholar
Joshi, P. P., Shegokar, V. R., Powar, R. M., Herder, S., Katti, R., Salkar, H. R., Dani, V. S., Bhargava, A., Jannin, J. and Truc, P. (2005). Human trypanosomiasis caused by Trypanosoma evansi in India: the first case report. American Journal of Tropical Medicine and Hygiene 73, 491–495.CrossRefGoogle ScholarPubMed
Krishnaiah, Y. S. P., Al-Saidan, S. M., Chandrasekar, D. V. and Satyanarayana, V. (2005). Bioavailability of nerolidol-based transdermal therapeutic system of nicorandil in human volunteers. Journal of Controlled Release 106, 111–122.CrossRefGoogle ScholarPubMed
Masocha, W., Robertson, B., Rottenberg, M. E., Mhlanga, J., Sorokin, L. and Kristensson, K. (2004). Cerebral vessel laminins and IFN-c define Trypanosoma brucei penetration of blood-barrier. Journal of Clinical Investigation 114, 689–694.CrossRefGoogle Scholar
Masocha, W., Rottenberg, M. and Kristensson, K. (2007). Migration of African trypanosomes across the BBB. Physiology & Behavior 92, 110–114.CrossRefGoogle Scholar
Nair, M., Jayant, R. D., Kaushik, A. and Sagar, V. (2016). Getting into the brain: potential of nanotechnology in the management of NeuroAIDS. Advanced Drug Delivery Reviews 103, 202–217.CrossRefGoogle ScholarPubMed
Oliveira, C. B., Rigo, L. A., Rosa, L. D., Gressler, L. T., Zimmermann, C. E., Ourique, A. F., Da Silva, A. S., Miletti, L. C., Beck, R. C. and Monteiro, S. G. (2014). Liposomes produced by reverse phase evaporation: in vitro and in vivo efficacy of diminazene aceturate against Trypanosoma evansi . Parasitology 141, 761–769.Google Scholar
Petry, B., Bootz, A., Khalansky, A., Hekmatara, T., Muller, R., Uhl, R., Kreuter, J. and Gelperina, S. (2007). Chemoterapy of brain tumor using doxorubicin bound to surfactant-coated poly (butyl cyanoacrylate) nanoparticles: revisiting the role of surfactants. Journal of Controlled Release 117, 51–58.CrossRefGoogle Scholar
Pinto, M. P., Arce, M., Yameen, B. and Vilos, C. (2017). Targeted brain delivery nanoparticles for malignant gliomas. Nanomedicine 12, 59–72.Google Scholar
Rempe, R., Cramer, S., Qiao, R. and Galla, H. J. (2014). Strategies to overcome the barrier: use of nanoparticles as carriers and modulators of barrier properties. Cell and Tissue Research 355, 717–726.Google Scholar
Rodrigues, A., Fighera, R. A., Souza, T. M., Schild, A. L., Soares, M. P., Milano, J. and Barros, C. S. L. (2005). Outbreaks of trypanosomosis in horses by Trypanosoma evansi in the state of Rio Grande do Sul, Brazil: epidemiological, clinical, hematological, and pathological aspects. Pesquisa Veterinária Brasileira 25, 239–249.CrossRefGoogle Scholar
Rodrigues, A., Fighera, R. A., Souza, T. M., Schild, A. L. and Barros, C. S. L. (2009). Neuropathology of naturally occurring Trypanosoma evansi infection of horses. Veterinary Pathology 46, 251–258.CrossRefGoogle ScholarPubMed
Silva, R. A. M. S., Seidl, A., Ramirez, L. and Dávila, A. M. R. (2002). Trypanosoma evansi e Trypanosoma vivax: Biologia, Diagnóstico e controle, Corumbá, Embrapa Pantanal.Google Scholar
Trevisan, G., Rossato, M. F., Tonello, R., Hoffmeister, C., Klafke, J. Z., Rosa, F., Pinheiro, K. V., Pinheiro, F. V., Boligon, A. A., Athayde, M. L. and Ferreira, J. (2014). Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice. Naunyn-Schmiedeberg's Archives of Pharmacology 987, 679–689.CrossRefGoogle Scholar
Ueno, N. and Lodoen, M. B. (2015). From the blood to the brain: avenues of eukaryotic pathogen dissemination to the central nervous system. Current Opinion in Microbiology 26, 53–59.CrossRefGoogle Scholar
Vitouley, H. S., Sidibe, I., Bengaly, Z., Marcotty, T., Abbeele, V. D. and Delespaux, V. (2012). Is trypanocidal drug resistance a threat for livestock health and production in endemic areas? Food for thoughts from Sahelian goats infected by Trypanosoma vivax in Bobo Dioulasso (Burkina Faso). Veterinary Parasitology 190, 349–354.Google Scholar
Want, M. Y., Yadav, P. and Afrin, F. (2016). Nanomedicines for therapy of visceral leishmaniasis. Journal of Nanoscience and Nanotechnology 16, 2143–2151.CrossRefGoogle ScholarPubMed
Wen, M. M., El-Salamouni, N. S., El-Refaie, W. M., Hazzah, H. A., Ali, M. M., Tosi, G., Farid, R. M., Blanco-Pietro, M. J., Billa, N. and Hanafy, A. S. (2017). Nanotechnology-based drug delivery systems for Alzheimer's disease: technical, industrial, and clinical challenges. Journal of Controlled Release 245, 95–107.CrossRefGoogle ScholarPubMed
Xia, X., Liu, H., Lv, H., Zhang, J., Zhou, J. and Zhao, Z. (2017). Preparation, characterization, and in vitro/vivo studies of oleanolic acid-loaded lactoferrin nanoparticles. Drugs Development and Therapeutics 2017, 1417–1427.CrossRefGoogle Scholar
Zhang, Z. and Feng, S. (2006). In vitro investigation of poly (lactide)-Tween 80 copolymer nanoparticles fabricated by dialysis method for chemotherapy. Biomacromolecules 7, 1139–114.CrossRefGoogle ScholarPubMed