Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-24T19:02:54.116Z Has data issue: false hasContentIssue false

Nanoencapsulation of benznidazole in calcium carbonate increases its selectivity to Trypanosoma cruzi

Published online by Cambridge University Press:  12 April 2018

Louise Donadello Tessarolo
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Ramon Róseo Paula Pessoa Bezerra de Menezes
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Clarissa Perdigão Mello
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Dânya Bandeira Lima
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Emanuel Paula Magalhães
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Eveline Matias Bezerra
Affiliation:
Departamento de Ciências Naturais, Matemática e Estatística, Universidade Federal Rural do Semi-Árido, Mossoró, Rio Grande do Norte, Brasil
Francisco Adilson Matos Sales
Affiliation:
Departamento de Ensino, Instituto Federal de Educação, Ciência e Tecnologia do Ceará, Aracati, CE, Brasil
Ito Liberato Barroso Neto
Affiliation:
Laboratório de Ciências e Tecnologia dos Materias, Departamento de Física, Universidade Federal do Ceará, Centro de Ciências, Fortaleza, CE, Brasil
Maria de Fátima Oliveira
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Ricardo Pires dos Santos
Affiliation:
Departamento de Engenharia da Computação, Universidade Federal do Ceará, Sobral, Ceará, Brazil
Eudenilson L. Albuquerque
Affiliation:
Departmento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brasil
Valder Nogueira Freire
Affiliation:
Laboratório de Ciências e Tecnologia dos Materias, Departamento de Física, Universidade Federal do Ceará, Centro de Ciências, Fortaleza, CE, Brasil
Alice Maria Martins*
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
*
Author for correspondence: Alice Maria Martins, E-mail: [email protected]

Abstract

Chagas disease is a public health problem, affecting about 7 million people worldwide. Benznidazole (BZN) is the main treatment option, but it has limited effectiveness and can cause severe adverse effects. Drug delivery through nanoparticles has attracted the interest of the scientific community aiming to improve therapeutic options. The aim of this study was to evaluate the cytotoxicity of benznidazole-loaded calcium carbonate nanoparticles (BZN@CaCO3) on Trypanosoma cruzi strain Y. It was observed that BZN@CaCO3 was able to reduce the viability of epimastigote, trypomastigote and amastigote forms of T. cruzi with greater potency when compared with BZN. The amount of BZN necessary to obtain the same effect was up to 25 times smaller when loaded with CaCO3 nanoparticles. Also, it was observed that BZN@CaCO3 enhanced the selectivity index. Furthermore, the cell-death mechanism induced by both BZN and BZN@CaCO3 was evaluated, indicating that both substances caused necrosis and changed mitochondrial membrane potential.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adade, CM, Chagas, GSF and Souto-Padrón, T (2012) Apis mellifera venom induces different cell death pathways in Trypanosoma cruzi. Parasitology 139(11), 14441461. http://doi.org/10.1017/S0031182012000790.Google Scholar
Bezerra, EM, Bezerra-Neto, JR, Sales, FAM, Santos, RPD, Martins, AMC, De Lima-Neto, P, Caetano, EWS, Albuquerque, EL and Freire, VN (2014) Optical absorption of the antitrypanocidal drug benznidazole inwater. Molecules 19(4), 41454156. http://doi.org/10.3390/molecules19044145.Google Scholar
Borges, AR, Aires, JRDA, Higino, TMM, Medeiros, MDGF De, Citó, AMDGL, Lopes, JAD and Figueiredo, RCBQ De (2012) Trypanocidal and cytotoxic activities of essential oils from medicinal plants of Northeast of Brazil. Experimental Parasitology 132(2), 123128. http://doi.org/10.1016/j.exppara.2012.06.003.Google Scholar
Branquinho, RT, Mosqueira, VCF, de Oliveira-Silva, JCV, Simões-Silva, MR, Saúde-Guimarães, DA and de Lana, M (2014) Sesquiterpene lactone in nanostructured parenteral dosage form is efficacious in experimental Chagas disease. Antimicrobial Agents and Chemotherapy 58(4), 20672075. http://doi.org/10.1128/AAC.00617-13.Google Scholar
Cheang, T, Wang, S, Hu, Z, Xing, Z, Chang, G, Yao, C, Liu, Y and Xu, A (2010) Calcium carbonate/CaIP6 nanocomposite particles as gene delivery vehicles for human vascular smooth muscle cells. Journal of Materials Chemistry 20, 80508055. http://doi.org/10.1039/C0JM00852D.Google Scholar
Fujiwara, M, Shiokawa, K, Morigaki, K, Zhu, Y and Nakahara, Y (2008) Calcium carbonate microcapsules encapsulating biomacromolecules. Chemical Engineering Journal 137, 1422. https://doi.org/10.1016/j.cej.2007.09.010.Google Scholar
Hasslocher-moreno, AM, Brasil, PEAA, Sousa, AS, Xavier, SS, Chambela, MC and Sperandio, GM (2012) Safety of benznidazole use in the treatment of chronic Chagas’ disease. Journal of Antimicrobial Chemotherapy 67(5), 12611266. https://doi.org/10.1093/jac/dks027.Google Scholar
Hernández-Chinea, C, Carbajo, E, Sojo, F, Arvelo, F, Kouznetsov, VV, Romero-Bohórquez, AR and Romero, PJ (2015) In vitro activity of synthetic tetrahydroindeno[2,1-c]quinolines on Leishmania mexicana. Parasitology International 64(6), 479483. http://doi.org/10.1016/j.parint.2015.06.011Google Scholar
Higaki, MDM, Kameyama, BSM, Udagawa, BSM, Ueno, MSY, Yamaguchi, Y, Igarashi, R, Ishihara, T and Mizushima, YMD (2006) Transdermal delivery of CaCO3 -nanoparticles containing insulin. Diabetes Technology & Therapeutics 8(3), 369374. https://doi.org/10.1016/j.cej.2007.09.010.Google Scholar
Krysko, DV, Vanden Berghe, T, Herde, KD and Vandenabeele, P (2008) Apoptosis and necrosis: detection, discrimination and phagocytosis. Science Direct 44, 205221. http://doi.org/10.1016/j.ymeth.2007.12.001.Google Scholar
Lee, J-A, Kim, M-K, Kim, H-M, Lee, JK, Jeong, J, Kim, Y-R, Oh, J-M and Choi, S-J (2015) The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices. International Journal of Nanomedicine 10, 22732293.Google Scholar
Lidani, KCF, Bavia, L, Ambrosio, AR, De Messias-reason, IJ and Barbosa, AS (2017) The complement system: a prey of Trypanosoma cruzi. Frontiers in Microbiology 8, 114. http://doi.org/10.3389/fmicb.2017.00607.Google Scholar
Manuja, A, Kumar, S, Dilbaghi, N, Kumar, R, Manuja, BK and Singh, SK (2013) Quinapyramine sulfate-loaded sodium alginate nanoparticles show enhanced trypanocidal activity. Nanomedicine: Nanotechnology, Biology, and Medicine 9, 16251634. http://doi.org/10.2217/NNM.13.148.Google Scholar
Marín, C, Ramírez-Macías, I, Rosales, MJ, Muro, B, Reviriego, F, Navarro, P, Aran, VJ and Sánchez-Moreno, M (2015) In vitro leishmanicidal activity of 1,3-disubstituted 5-nitroindazoles. Acta Tropica 148, 170178. http://doi.org/10.1016/j.actatropica.2015.04.028.Google Scholar
Martins-Melo, FR, Ramos, AN, Alencar, CH and Heukelbach, J (2014) Prevalence of Chagas disease in Brazil: a systematic review and meta-analysis. Acta Tropica 130(1), 167174. http://doi.org/10.1016/j.actatropica.2013.10.002.Google Scholar
Maya, JD, Cassels, BK, Iturriaga-vásquez, P, Ferreira, J, Faúndez, M, Galanti, N, Ferreira, A and Morello, A (2007) Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comparative Biochemistry and Physiology 146, 601620. http://doi.org/10.1016/j.cbpa.2006.03.004.Google Scholar
Meira, CS, Guimarães, ET, Santos, JAF, Moreira, DRM, Nogueira, RC, Tomassini, TCB, Ribeiro, IM, Souza, CVC, Santos, RR and Soares, MBP (2015) In vitro and in vitro antiparasitic activity of Physalis angulata L. concentrated ethanolic ethanolic extract against Trypanosoma cruzi. Phytomedicine 22, 969974. http://doi.org/10.1016/j.phymed.2015.07.004.Google Scholar
Mondal, S, Roy, P, Das, S, Halder, A, Mukherjee, A and Bera, T (2013) In vitro susceptibilities of wild and drug resistant Leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin E derivative TPGS for nanoparticle efficacy. PLoS ONE 8(12), e81492. http://doi.org/10.1371/journal.pone.0081492.Google Scholar
Morilla, MJ and Romero, EL (2015) Nanomedicines against Chagas disease: an update on therapeutics, prophylaxis and diagnosis. Nanomedicine: Nanotechnology, Biology, and Medicine 10, 465481.Google Scholar
Nogueira, NP, Saraiva, FMS, Sultano, PE, Cunha, PRBB, Laranja, GAT, Justo, GA, Sabino, KCC, Coelho, MGP, Rossini, A, Atella, GC and Paes, MC (2015) Proliferation and differentiation of Trypanosoma cruzi inside its vector have a new trigger: redox status. PLoS ONE 10(2), e0116712. http://doi.org/10.1371/journal.pone.0116712.Google Scholar
Qian, K, Shi, T, Tang, T, Zhang, S, Liu, X and Cao, Y (2011) Preparation and characterization of nano-sized calcium carbonate as controlled release pesticide carrier for validamycin against Rhizoctonia solani. Microchim Acta 173, 5157.Google Scholar
Rassi, A and Marin-Neto, JA (2010) Chagas disease. Lancet 375(9723), 13881402. http://doi.org/10.1016/S0140-6736(10)60061-X.Google Scholar
Ribeiro, TG, Chávez-Fumagall, MA, Valadares, DG, França, JR, Rodrigues, LB, Duarte, MC, Lage, PS, Andrade, PHR, Lage, DP, Arruda, LV, Abanades, DR, Costa, LE, Martins, VT, Tavares, CAP, Castilho, RO, Coelho, EAF and Faraco, AAG (2014) Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system. International Journal of Nanomedicine 9(1), 877890. http://doi.org/10.2147/IJN.S55678.Google Scholar
Romero, EL and Morilla, MJ (2010) Nanotechnological approaches against Chagas disease. Advanced Drug Delivery Reviews 62(4–5), 576588. http://doi.org/10.1016/j.addr.2009.11.025.Google Scholar
Sánchez, G, Cuellar, D, Zulantay, I, Gajardo, M and González-Martin, G (2002) Cytotoxicity and trypanocidal activity of nifurtimox encapsulated in ethylcyanoacrylate nanoparticles. Biological Research 35(1), 3945.Google Scholar
Sharma, S, Verma, A, Teja, BV, Pandey, G, Mittapelly, N, Trivedi, R and Mishra, PR (2015) An insight into functionalized calcium based inorganic nanomaterials in biomedicine: trends and transitions. Colloids and Surfaces B: Biointerfaces 133, 120139. http://doi.org/10.1016/j.colsurfb.2015.05.014.Google Scholar
Sousa, PL, Oliveira, R, Tessarolo, LD, Menezes, RRPPB, Sampaio, TL, Canuto, JA and Martins, AMC (2017) Betulinic acid induces cell death by necrosis in Trypanosoma cruzi. Acta Tropica 174, 7275. http://doi.org/10.1016/j.actatropica.2017.07.003.Google Scholar
Unciti-Broceta, JD, Arias, JL, Maceira, J, Soriano, M, Ortiz-González, M, Hernández-Quero, J, Munoz-Torres, M, Koning, HP, Magez, S and Garcia-Salcedo, JA (2015) Specific cell targeting therapy bypasses drug resistance mechanisms in African Trypanosomiasis. PLoS Pathogens 11(6), e1004942. http://doi.org/10.1371/journal.ppat.1004942.Google Scholar
Van de Ven, H, Vermeersch, M, Matheeussen, A, Vandervoort, J, Weyenberg, W, Apers, S, Cos, P, Maes, L and Ludwig, A (2011) PLGA nanoparticles loaded with the antileishmanial saponin β-aescin: factor influence study and in vitro efficacy evaluation. International Journal of Pharmaceutics 420(1), 122132. http://doi.org/10.1016/j.ijpharm.2011.08.016.Google Scholar
Vendrametto, MC, Santos, AOD, Nakamura, CV, Dias Filho, BP, Cortez, DAG and Ueda-Nakamura, T (2010) Evaluation of antileishmanial activity of eupomatenoid-5, a compound isolated from leaves of Piper regnellii var. pallescens. Parasitology International 59(2), 154158. http://doi.org/10.1016/j.parint.2009.12.009.Google Scholar
Waypa, GB, Smith, KA and Schumacker, PT (2016) O2 sensing, mitochondria and ROS signaling: the fog is lifting. Molecular Aspects of Medicine 47, 114. http://doi.org/10.1016/j.mam.2016.01.002.Google Scholar
Wei, W, Ma, G, Hu, G, Yu, D, Mcleish, T, Su, Z and Shen, Z (2010) Preparation of hierarchical hollow CaCO3 particles and the application as anticancer drug carrier. Journal of the American Chemical Society 130, 1580815810. http://doi.org/10.1021/ja8039585.Google Scholar
Wen, R, Banik, B, Pathak, RK, Kumar, A, Kolishetti, N and Dhar, S (2016) Nanotechnology inspired tools for mitochondrial dysfunction related diseases. Advanced Drug Delivery Reviews 99, Part A, 5269. http://doi.org/10.1016/j.addr.2015.12.024.Google Scholar
WHO (2015) World Health Organization. Chagas disease (American trypanosomiasis). Fact Sheet, n.340. http://who.int/mediacentre/factsheets/fs340/en/.Google Scholar
Yang, J, Li, F, Li, M, Zhang, S, Liu, J, Liang, C and Sun, Q (2017) Fabrication and characterization of hollow starch nanoparticles by gelation process for drug delivery application. Carbohydrate Polymers 173, 223232. http://doi.org/10.1016/j.carbpol.2017.06.006.Google Scholar
Zazo, H, Colino, CI and Lanao, JM (2016) Current applications of nanoparticles in infectious diseases. Journal of Controlled Release 224, 86102. http://doi.org/10.1016/j.jconrel.2016.01.008.Google Scholar
Zhao, Y, Lu, Y, Hu, Y, Li, J, Dong, L and Lin, L (2010) Synthesis of superparamagnetic CaCO3 mesocrystals for multistage delivery in cancer therapy. Small 6(21), 24362442. http://doi.org/10.1002/smll.201000903.Google Scholar