Abstract
Paracoccidioidomycosis (PCM) is a disease caused by fungi of the genus Paracoccidioides. The disease is responsible for high rates of premature deaths and socioeconomic repercussions. The limitations of antifungal agents against PCM have motivated the search for new compounds. In our ongoing exploration of Cerrado plants as potential sources of new antifungal agents, we selected Copaifera langsdorffii oil (Copaíba resin oil) in order to explore its bioactive potential and test a formulation to increase oil stability and solubilization employing Pluronic F-127 to obtain the nanoemulsion of the oil. We aim at testing both Copaíba resin oil and its nanoemulsion against four species of the Paracoccidioides genus. We performed cytotoxicity test in Balb/C3T3 cells, hemolytic activity and interaction of Copaíba resin oil and Copaíba resin oil nanoemulsion (CopaPlu) with the antifungal agents such as amphotericin B, co-trimoxazole, and itraconazole. Moreover, the Copaíba resin oil was analyzed by mass spectrometry to identify its chemical profile. Eventually, a new methodology to prepare the nanoemulsion is presented. The Copaíba resin oil and CopaPlu nanoemulsion inhibited Paracoccidioides sp. growth efficiently, and no cytotoxicity or hemolytic effect was observed at minimum inhibitory concentration (MIC). When combined with amphotericin B, Copaíba resin oil and its nanoemulsion showed an additive effect with reduction of MIC values. The Copaíba resin oil and CopaPlu nanoemulsion is a promising antifungal agent against Paracoccidioides.
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References
Denning DW, Bromley MJ (2015) How to bolster the antifungal pipeline. Science 347:1414–1416. https://doi.org/10.1126/science.aaa6097
Shikanai-Yasuda MA, Mendes RP, Colombo AL, Queiroz-Telles F de, Kono ASG, Paniago AMM, Nathan A, do Valle ACF , Bagagli E, Benard G, Ferreira MS, de Teixeira MM, Silva-Vergara ML, Pereira RM, Cavalcante R de S, Hahn R, Durlacher RR, Khoury Z, Camargo ZP de, Moretti ML, Martinez R. (2017). Brazilian guidelines for the clinical management of paracoccidioidomycosis. Rev Soc Bras Med Trop 50: 715–740. https://doi.org/10.5123/s1679-49742018000500001
Martinez R (2015) Epidemiology of Paracoccidioidomycosis. Rev Inst Med Trop São Paulo 57:11–20. https://doi.org/10.1590/S0036-46652015000700004
Zambuzzi-Carvalho P, Tomazett P, Santos S, Ferri P, Borges C, Martins W, de Almeida Soares C, Pereira M (2013) Transcriptional profile of Paracoccidioides induced by oenothein B, a potential antifungal agent from the Brazilian Cerrado plant Eugenia uniflora. BMC Microbiol 13:227. https://doi.org/10.1186/1471-2180-13-227
Do Carmo LS, Tamayo Ossa DP, da Castro SVC, Bringel Pires L, de Alves Oliveira CM, da Conceição Silva C, Coelho NP, Bailão AM, Parente-Rocha JA, de Soares CMA, Ruiz OH, Ochoa JGM, Pereira M (2015) Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative. PLoS One 10:e0130703. https://doi.org/10.1371/journal.pone.0130703
Amaral AC, Bocca AL, Ribeiro AM, Nunes J, Peixoto DLG, Simioni AR, Primo FL, Lacava ZGM, Bentes R, Titze-de-Almeida R, Tedesco AC, Morais PC, Felipe MSS (2009) Amphotericin B in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles against paracoccidioidomycosis. J Antimicrob Chemother 63:526–533. https://doi.org/10.1093/jac/dkn539
Overbeck G, Muller S, Fidelis A, Pfadenhauer J, Pillar V, Blanco C, Boldrini I, Both R, Forneck E (2007) Brazil’s neglected biome: the South Brazilian Campos. Persp Plant Ecol Evol System 9:101116. https://doi.org/10.1016/j.ppees.2007.07.005
Dutra RC, Campos MM, Santos ARS, Calixto JB (2016) Medicinal plants in Brazil: pharmacological studies, drug discovery, challenges and perspectives. Pharm Res 112:4–29. https://doi.org/10.1016/j.phrs.2016.01.021
da Trindade R, da Silva J, Setzer W (2018) Copaifera of the Neotropics: a review of the phytochemistry and pharmacology. Int J Mol Sci 19:1511. https://doi.org/10.3390/ijms19051511
Jahangirian H, Ghasemian Lemraski E, Webster TJ, Rafiee-Moghaddam R, Abdollahi Y (2017) A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine. Int J Nanomedicine 12:2957–2978. https://doi.org/10.2147/IJN.S127683
Silva LC, Neves BJ, Gomes MN, Melo-Filho CC, Soares CM, Andrade CH, Pereira M (2018) Computer-aided identification of novel anti-paracoccidioidomycosis compounds. Future Microbiol 13:1523–1535. https://doi.org/10.2217/fmb-2018-0175
Johnson MD, MacDougall C, Ostrosky-Zeichner L, Perfect JR, Rex JH (2004) Combination antifungal therapy. Antimicrob Agents Chemother 48:693–715. https://doi.org/10.1128/AAC.48.3.693-715.2004
Wu H, Zhong Q, Zhong R, Huang H, Xia Z, Ke Z, Zhang Z, Song J, Jia X (2016) Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment. Int J Nanomedicine 11:6337–6352. https://doi.org/10.2147/IJN.S119839
Hahn RC, Morato Conceição YT, Santos NL, Ferreira JF, Hamdan JS (2003) Disseminated paracoccidioidomycosis: correlation between clinical and in vitro resistance to ketoconazole and trimethoprim sulphamethoxazole. Mycoses 46:342–347. https://doi.org/10.1046/j.1439-0507.2003.00901.x
Gupta D, Jain D (2015) Chalcone derivatives as potential antifungal agents: synthesis, and antifungal activity. J Adv Pharm Tech Res 6:114. https://doi.org/10.4103/2231-4040.161507
Veiga Junior VF, Rosas EC, Carvalho MV, Henriques MGMO, Pinto AC (2007) Chemical composition and anti-inflammatory activity of copaiba oils from Copaifera cearensis Huber ex Ducke, Copaifera reticulata Ducke and Copaifera multijuga Hayne--a comparative study. J Ethnopharmacol 112:248–254. https://doi.org/10.1016/j.jep.2007.03.005
de Gomes NM, de Rezende CM, Fontes SP, Hovell AMC, Landgraf RG, Matheus ME, da Pinto AC, Fernandes PD (2008) Antineoplastic activity of Copaifera multijuga oil and fractions against ascitic and solid Ehrlich tumor. J Ethnopharmacol 119:179–184. https://doi.org/10.1016/j.JEP.2008.06.033
Abrão F, de Araújo Costa LD, Alves JM, Senedese JM, de Castro PT, Ambrósio SR, Veneziani RCS, Bastos JK, Tavares DC, Martins CHG (2015) Copaifera langsdorffii oleoresin and its isolated compounds: antibacterial effect and antiproliferative activity in cancer cell lines. BMC Compl Alternative Med 15:443. https://doi.org/10.1186/s12906-015-0961-4
Zimmermam-Franco D, Bolutari E, Polonini H, do Carmo A, Graças AM, das Chaves M, Raposo N (2013) Antifungal activity of Copaifera langsdorffii Desf oleoresin against dermatophytes. Molecules 18:12561–12570. https://doi.org/10.3390/molecules181012561
Deus RJ, Alves C, Arruda MS (2011) Avaliação do efeito antifúngico do óleo resina e do óleo essencial de copaíba (Copaifera multijuga Hayne). Rev Bras Plant Med 13:01–07. https://doi.org/10.1590/S1516-05722011000100001
Harmsen S, McLaren AC, Pauken C, McLemore R (2011) Amphotericin B is cytotoxic at locally delivered concentrations. Clin Orth Related Res 469:3016–3021. https://doi.org/10.1007/s11999-011-1890-2
Svetlichny G, Külkamp-Guerreiro IC, Cunha SL, Silva FEK, Bueno K, Pohlmann AR, Fuentefria AM, Guterres SS (2015) Solid lipid nanoparticles containing copaiba oil and allantoin: development and role of nanoencapsulation on the antifungal activity. Pharmazie 70:155–164. https://doi.org/10.1691/ph.2015.4116
Alencar ÉN, Xavier-Júnior FH, Morais ARV, Dantas TRF, Dantas-Santos N, Verissimo LM, Rehder VLG, Chaves GM, Oliveira AG, Egito EST (2015) Chemical characterization and antimicrobial activity evaluation of natural oil nanostructured emulsions. J Nanoscience Nanotech 15:880–888. https://doi.org/10.1166/jnn.2015.9187
Khattak SF, Bhatia SR, Roberts SC (2005) Pluronic F127 as a cell encapsulation material: utilization of membrane-stabilizing agents. Tissue Eng 11:974–983. https://doi.org/10.1089/ten.2005.11.974
Ai X, Zhong L, Niu H, He Z (2014) Thin-film hydration preparation method and stability test of DOX-loaded disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate nanomicelles. Asian J Pharm Sciences 9:244–250. https://doi.org/10.1016/j.ajps.2014.06.006
Shar JA, Obey TM, Cosgrove T (1998) Adsorption studies of polyethers Part 1. Adsorption onto hydrophobic surfaces. Colloids Surf A: Phys Engin Aspects 136:2133. https://doi.org/10.1016/S0927-7757(97)00182-9
Burt S (2004) Essential oils: their antibacterial properties and potential applications in foods − a review. Int J Food Microbiol 94:223–253. https://doi.org/10.1016/j.ijfoodmicro.2004.03.022
Amin K, Dannenfelser RM (2006) In vitro hemolysis: guidance for the pharmaceutical scientist. J Pharm Sci 95:1173–1176. https://doi.org/10.1002/jps.20627
Aparicio RM, José García-Celma M, Pilar Vinardell M, Mitjans M (2005) In vitro studies of the hemolytic activity of microemulsions in human erythrocytes. J Pharm Biomed Anal 39:1063–1067. https://doi.org/10.1016/j.jpba.2005.06.013
Cuenca-Estrella M (2004) Combinations of antifungal agents in therapy-what value are they? J Antimicrob Chemother 54:854869. https://doi.org/10.1093/jac/dkh434
Sherweit E-A, Mohamed E-S, Rola M (2013) The synergetic efficacy of the combination of amphotericin B and certain essential oils against selected fungal clinical isolates. J Applied Pharm Science 3:26–30. https://doi.org/10.7324/JAPS.2013.3404
Funding
This work was performed at Universidade Federal de Goiás supported by MCTI/CNPq (Ministério da Ciência e Tecnologia/Conselho Nacional de Desenvolvimento Científico e Tecnológico), FNDCT (Fundo Nacional de Desenvolvimento Científico e Tecnológico), FAPEG (Fundação de Amparo à Pesquisa do Estado de Goiás), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ Finance Code 001), FINEP (Financiadora de Estudos e Projetos), PRONEX (Programa de Apoio a Núcleos de Excelência) and INCT-IF (Instituto Nacional de Ciência e Tecnologia para Inovação Farmacêutica). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Each author has contributed significantly to this work. FSE and AFR performed the extraction and identification of Copaíba resin oil. LCS and MACM performed biological analysis and share the first authorship. JVF, SFAF, and ECOL performed the preparation and analysis of the nanoemulsion Copaíba resin. LK, APT, and CMAO performed the characterization of the components of the Copaíba resin oil, and LCS, MACM, CMAS, MP, CMAO, and LK analyzed the data and wrote the paper.
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do Carmo Silva, L., Miranda, M.A.C.M., de Freitas, J.V. et al. Antifungal activity of Copaíba resin oil in solution and nanoemulsion against Paracoccidioides spp.. Braz J Microbiol 51, 125–134 (2020). https://doi.org/10.1007/s42770-019-00201-3
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DOI: https://doi.org/10.1007/s42770-019-00201-3