Neglected diseases and pharmaceutical industry: the case of Chagas Disease

Authors

DOI:

https://doi.org/10.33448/rsd-v10i2.12419

Keywords:

Neglected Diseases; Chagas Disease; Drug development.

Abstract

The development of new active ingredients in the context of Neglected Tropical Diseases (NTDs), remains a big challenge to the society. Among NTDs it is worth highlight the Chagas disease (CD) which has high morbidity and mortality. This study aims to retrieve information about the current scenario as well as new strategies and innovations in the pharmacological treatment of CD. For this purpose, a narrative review was conducted in which the articles were selected in PubMed, SciELO and LILACS, in the period between 2015/2020. Seeking to assess in order of relevance in academia the data were observed in results of publications in the SciELO between 1950/2019, about CD, diabetes mellitus and cancer. Information on clinical trials was also searched at ClinicalTrials.gov. In the last 20 years the number of publications on CD in SciELO was significantly lower compared to diabetes mellitus and cancer. Moreover, only two drugs are available, benznidazole and nifurtimox, which have limitations such as the amount of adverse effects. Therefore, new therapeutic options have been studied mainly in the case of benznidazole and have shown promising results by optimizing toxicity, absorption and bioavailability, for example. With regard to clinical trials, a total of seven studies were found, which investigate five compounds for the treatment of CD. Only one of the compounds has no clinical use yet, selenium, which suggests a deficiency in the search for new drug candidates. Such information reinforces, therefore, the neglected character of CD, as well as emphasizing the importance of researching new therapies.

References

Alencar, M. M. F., Santos Filho, R. A. B., Hirschheiter, C. Â., Carmo, M. C. N., Santana, M. S., Ramos, J. L. D., ... & Galvão, P. V. M. (2020). Epidemiologia da Doença de Chagas aguda no Brasil de 2007 a 2018. Research, Society and Development, 9(10), e8449109120-e8449109120. https://doi.org/10.33448/rsd-v9i10.9120.

Alves-Silva, I., Marreto, R. N., Gelfuso, G. M., Sá-Barreto, L. C. L., Lima, E. M., & Cunha-Filho, M. S. S. (2016). Preparation of benznidazole pellets for immediate drug delivery using the extrusion spheronization technique. Drug Development and Industrial Pharmacy, 43(5), 762-769. http://dx.doi.org/10.1080/03639045.2016.1220574.

Araújo, J. M. D., Silva, A. P., Cândido, M. B., Silva, T. W. M., & Andrade Júnior, F. P. (2020). Estudo etnofarmacológico de Anacardium occidentale: uma breve revisão. Research, Society and Development, 9(8), e487985802-e487985802. http://dx.doi.org/10.33448/rsd-v9i8.8502.

Bermudez, J., Davies, C., Simonazzi, A., Real, J. P., & Palma, S. (2016). Current drug therapy and pharmaceutical challenges for Chagas disease. Acta Tropica, 156, 1-16. http://dx.doi.org/10.1016/j.actatropica.2015.12.017.

Branquinho, R. T., Pound-Lana, G., Milagre, M. M., Saúde-Guimarães, D. A., Vilela, J. M. C., Andrade, M. S., ... & Mosqueira, V. C. F. (2017). Increased Body Exposure to New Anti-Trypanosomal Through Nanoencapsulation. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-08469-x.

Brasil, Agência Nacional de Vigilância Sanitária. (2020a). Câmara de Regulação do Mercado de Medicamentos- CMED. Disponível em: <http://antigo.anvisa.gov.br/documents/374947/6048620/LISTA_CONFORMIDADE_2020_10_v1.pdf/7b88a38f-1b2f-4768-b589-f62b4beb1762>. Acesso em: 10 nov. 2020.

Brasil, Agência Nacional de Vigilância Sanitária. (2020b). Bulário eletrônico. Disponível em: <https://consultas.anvisa.gov.br/#/bulario/>. Acesso em: 25 nov. 2020.

Cruz, C. A. B., Silva, A. L. S., Alencar, E. M. D., Santos, N. J. B., Moreira, J. J. S., Paixão, A. E. A., & Gomes, I. M. A. (2016). Tecnologias que empregam fármacos antiparasitários para tratamento da doença Chagas. Revista Eletrônica de Comunicação, Informação e Inovação em Saúde, 10(1), 1-9. https://doi.org/10.29397/reciis.v10i1.1075.

Cummings, J., Lee, G., Riitter, A., & Zhong, K. (2018). Alzheimer's disease drug development pipeline: 2018. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 4, 195-214. https://doi.org/10.1016/j.trci.2018.03.009.

Dawidowski, M., Kalel, V. C., Napolitano, V., Fino, R., Schorpp, K., Emmanouilidis, L., ... & Popowicz, G. M. (2020). Structure−Activity Relationship in Pyrazolo[4,3 c]pyridines, First Inhibitors of PEX14−PEX5 Protein−Protein Interaction with Trypanocidal Activity. Journal of Medicinal Chemistry, 63, 847−879. https://doi.org/10.1021/acs.jmedchem.9b01876.

Dias, J. C. P., Ramos Jr, A. N., Gontijo, E. D., Luquetti, A., Shikanai-Yasuda, M. A., Coura, J. R., ... & Alves, R. V. (2016). Consenso Brasileiro em Doença de Chagas, 2015. Epidemiologia e Serviços de Saúde, 25(esp.), 7-86. https://doi.org/10.5123/S1679-49742016000500002.

DrugBank. 2020. Benznidazole – DrugBank. Disponível em: <https://go.drugbank.com/drugs/DB11989>. Acesso em: 18 nov. 2020.

DrugBank. 2020. Nifurtimox – DrugBank. Disponível em: <https://go.drugbank.com/drugs/DB11820>. Acesso em: 20 nov. 2020.

García, M. C., Manzo, R. H., & Jimenez-Kairuz, A. (2018). Polysaccharides-based multiparticulated interpolyelectrolyte complexes for controlled benznidazole release. International Journal of Pharmaceutics, 545(1-2), 366-377. https://doi.org/10.1016/j.ijpharm.2018.05.017.

García, M. C., Martinelli, M., Ponce, N. E., Sanmarco, L. M., Aoki, M. P., Manzo, R. H., & Jimenez-Kairuz, A. F. (2018). Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes. European Journal of Pharmaceutical Sciences, 120, 107-122. https://doi.org/10.1016/j.ejps.2018.04.034.

Harrer, S., Shah, P., Antony, B., & Hu, J. (2019). Artificial intelligence for clinical trial design. Trends in Pharmacological Sciences, 40(8), 577-591. https://doi.org/10.1016/j.tips.2019.05.005.

Lafepe, Laboratório Farmacêutico do Estado de Pernambuco. (2016). Guia de Compras do Benznidazol. Disponível em: <http://www.lafepe.pe.gov.br/wp-content/uploads/2016/08/Guia-de-Compras-BZD-27082010_revis%C3%A3o-Ago16.pdf>. Acesso em: 17 dez. 2020.

Martins-Melo, F. R., Carneiro, M., Ramos Jr, A. N., Heukelbach, J., Ribeiro, A. L. P., & Werneck, G. L. (2018). The burden of neglected tropical diseases in Brazil, 1990-2016: a subnational analysis from the Global Burden of Disease Study 2016. PLoS Neglected Tropical Diseases, 12(6), e0006559. https://doi.org/10.1371/journal.pntd.0006559.

Mello, C. G. C., Branquinho, R. T., Oliveira, M. T., Milagre, M. M., Mosqueira, V. C. F., & Lana, M. (2016). Efficacy of lychnopholide polymeric nanocapsules after oral and intravenous administration in murine experimental Chagas disease. Antimicrobial Agents and Chemotherapy, 60(9), 5215–5222. https://doi.org/10.1128/AAC.00178-16.

Oliveira, E. C. V., Carneiro, Z. A., Albuquerque, S., & Marchetti, J. M. (2017). Development and Evaluation of a Nanoemulsion Containing Ursolic Acid: a Promising Trypanocidal Agent. AAPS PharmSciTech, 18(7), 2551-2560. https://doi.org/10.1208/s12249-017-0736-y.

Pereira A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. [e-book]. Santa Maria. Ed. UAB/NTE/UFSM. Recuperado de: <https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1>. Acesso em: 03 fev. 2021.

Simonazzi, A., Davies, S., Cid, A. G., Gonzo, E., Parada, L., & Bermúdez, J. M. (2018). Preparation and Characterization of Poloxamer 407 Solid Dispersions as an Alternative Strategy to Improve Benznidazole Bioperformance. Journal of Pharmaceutical Sciences, 107, 2829-2836. https://doi.org/10.1016/j.xphs.2018.06.027.

Souza, H. F. S., Real, D., Leonardi, D., Rocha, S. C., Alonso, V., Serra, E., ... & Salomon, C. J. (2017) Development and in-vitro/in-vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach. Tropical Medicine & International Health, 22(12), 1514-1522. https://doi.org/10.1111/tmi.12980.

Umscheid, C. A., Margolis, D. J., & Grossman, C. E. (2011). Key concepts of clinical trials: a narrative review. Postgraduate Medicine, 123(5), 194-204. https://doi.org/10.3810/pgm.2011.09.2475.

Xue, H., Li, J., Xie, H., & Wang, Y. (2018). Review of drug repositioning approaches and resources. International Journal of Biological Sciences, 14(10), 1232-1244. https://doi.org/10.7150/ijbs.24612.

Weng, H.-B., Chen, H.-X., & Wang, M.-W. (2018). Innovation in neglected tropical disease drug discovery and development. Infectious Diseases of Poverty, 7(67), 1-9. https://doi.org/10.1186/s40249-018-0444-1.

Who – World Health Organization. (2020a). Neglected Tropical Diseases. Disponível em: https://www.who.int/news-room/q-a-detail/neglected-tropical-diseases. Acesso em: 23 nov. 2020.

Who – World Health Organization. (2020b). Chagas Disease. Disponível em: https://www.who.int/health-topics/chagas-disease#tab=tab_1. Acesso em: 24 nov. 2020.

Published

10/02/2021

How to Cite

SILVA, A. P. da .; DANTAS, G. M. S.; SILVA, P. I. F. da .; MEDEIROS, A. N. G. de .; NAGASHIMA JUNIOR, T. Neglected diseases and pharmaceutical industry: the case of Chagas Disease. Research, Society and Development, [S. l.], v. 10, n. 2, p. e21110212419, 2021. DOI: 10.33448/rsd-v10i2.12419. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/12419. Acesso em: 16 apr. 2024.

Issue

Section

Health Sciences