Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Silva, Bismarques Augusto Oliveira da lattes
Orientador(a): Silva, Fabrício Souza lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Estadual de Feira de Santana
Programa de Pós-Graduação: Doutorado Acadêmico em Biotecnologia
Departamento: DEPARTAMENTO DE TECNOLOGIA
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://tede2.uefs.br:8080/handle/tede/1916
Resumo: β-Myrcene is a monoterpene possessing anti-inflammatory, antioxidant, and antinociceptive properties. This study aimed to develop a myrcene-containing nanoemulsion (NEMC), evaluate its acute toxicity, and investigate the spasmolytic, antitussive, antiasthmatic, and expectorant effects of myrcene or the myrcene-containing nanoemulsion. NEMC was formulated using the spontaneous emulsification method. This involved adding an aqueous phase, consisting of a phosphate buffer solution, to an organic phase. The organic phase was composed of medium-chain triglyceride oil, myrcene, and surfactants in varying proportions, under constant stirring and at room temperature. The size and polydispersity index of the nanoemulsion were determined. This study was approved by the Ethics Committee on Animal Use of the Federal University of Vale do São Francisco (CEUA-UNIVASF), registered under No. 0002/270121. Preclinical acute toxicity was evaluated according to OECD guidelines. Each animal received a single oral dose of 2,000 mg/kg of NEMC and was observed at 30, 60, 120, 180, and 360 minutes, and every 24 hours for 14 days. Motor behavior and muscle relaxation in mice were assessed using open-field and rotarod tests. The spasmolytic activity on isolated rat tracheal smooth muscle was evaluated in an organ bath under carbachol or KCl-induced contractions. Antitussive activity was assessed using the citric acid-induced cough method. The antitussive activity of inhaled myrcene was also investigated. Expectorant activity was determined by quantifying phenol red. Antiasthmatic activity was evaluated using an ovalbumin (OVA)-induced asthma model. NEMC exhibited a size of 97.37±5.844 nm and a polydispersity index (PDI) of 0.2387±0.01810. Acute toxicity tests (2000 mg/kg, oral administration) showed no mortality or significant changes in physiological parameters. In experimental models, β-myrcene (75 mg/kg) did not affect motor coordination (open-field and rotarod tests) and induced modest relaxation (10.41±5.11% under carbachol contraction; 19.48±5.12% under KCl contraction) in isolated rat trachea. In its nanoemulsified form, NEMC (75 mg/kg) significantly reduced citric acid-induced cough frequency (55.62±16.48% vs. 121.2±9.41% of control; p < 0.05), with a mechanism involving GABAergic and opioid pathways, and potassium channels. Both formulations demonstrated expectorant activity, increasing phenol red secretion in bronchoalveolar lavage (NEMC: 3.38±0.29 µg/mL vs. 1.93±0.11 µg/mL for saline). In the ovalbumin-induced asthma model, NEMC significantly reduced the migration of inflammatory cells, confirming its antiasthmatic effect. These results indicate that the nanoemulsion preserves the pharmacological properties of β-myrcene, offering advantages in terms of bioavailability. Both formulations exhibited antitussive, expectorant, and anti-inflammatory effects, highlighting their therapeutic potential for respiratory diseases, particularly asthma and associated conditions. The study reveals the nanoemulsion as a promising strategy for delivering lipophilic compounds.
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spelling Silva, Fabrício Souzahttps://orcid.org/0000-0002-6394-6501http://lattes.cnpq.br/70616082081912491709626986626495http://lattes.cnpq.br/1709626986626495Silva, Bismarques Augusto Oliveira da2025-09-01T17:32:29Z2025-05-06SILVA, Bismarques Augusto Oliveira da. Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios, 2025, 112 f., Tese (doutorado) - Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana.http://tede2.uefs.br:8080/handle/tede/1916β-Myrcene is a monoterpene possessing anti-inflammatory, antioxidant, and antinociceptive properties. This study aimed to develop a myrcene-containing nanoemulsion (NEMC), evaluate its acute toxicity, and investigate the spasmolytic, antitussive, antiasthmatic, and expectorant effects of myrcene or the myrcene-containing nanoemulsion. NEMC was formulated using the spontaneous emulsification method. This involved adding an aqueous phase, consisting of a phosphate buffer solution, to an organic phase. The organic phase was composed of medium-chain triglyceride oil, myrcene, and surfactants in varying proportions, under constant stirring and at room temperature. The size and polydispersity index of the nanoemulsion were determined. This study was approved by the Ethics Committee on Animal Use of the Federal University of Vale do São Francisco (CEUA-UNIVASF), registered under No. 0002/270121. Preclinical acute toxicity was evaluated according to OECD guidelines. Each animal received a single oral dose of 2,000 mg/kg of NEMC and was observed at 30, 60, 120, 180, and 360 minutes, and every 24 hours for 14 days. Motor behavior and muscle relaxation in mice were assessed using open-field and rotarod tests. The spasmolytic activity on isolated rat tracheal smooth muscle was evaluated in an organ bath under carbachol or KCl-induced contractions. Antitussive activity was assessed using the citric acid-induced cough method. The antitussive activity of inhaled myrcene was also investigated. Expectorant activity was determined by quantifying phenol red. Antiasthmatic activity was evaluated using an ovalbumin (OVA)-induced asthma model. NEMC exhibited a size of 97.37±5.844 nm and a polydispersity index (PDI) of 0.2387±0.01810. Acute toxicity tests (2000 mg/kg, oral administration) showed no mortality or significant changes in physiological parameters. In experimental models, β-myrcene (75 mg/kg) did not affect motor coordination (open-field and rotarod tests) and induced modest relaxation (10.41±5.11% under carbachol contraction; 19.48±5.12% under KCl contraction) in isolated rat trachea. In its nanoemulsified form, NEMC (75 mg/kg) significantly reduced citric acid-induced cough frequency (55.62±16.48% vs. 121.2±9.41% of control; p < 0.05), with a mechanism involving GABAergic and opioid pathways, and potassium channels. Both formulations demonstrated expectorant activity, increasing phenol red secretion in bronchoalveolar lavage (NEMC: 3.38±0.29 µg/mL vs. 1.93±0.11 µg/mL for saline). In the ovalbumin-induced asthma model, NEMC significantly reduced the migration of inflammatory cells, confirming its antiasthmatic effect. These results indicate that the nanoemulsion preserves the pharmacological properties of β-myrcene, offering advantages in terms of bioavailability. Both formulations exhibited antitussive, expectorant, and anti-inflammatory effects, highlighting their therapeutic potential for respiratory diseases, particularly asthma and associated conditions. The study reveals the nanoemulsion as a promising strategy for delivering lipophilic compounds.O β-mirceno é um monoterpeno com propriedades anti-inflamatórias, antioxidantes e antinociceptivas. Este tabalho teve como objetivos: desenvolver uma nanoemulsão contendo mirceno (NEMC); avaliar a toxicidade aguda da nanoemulsão e investigar os efeitos espasmolítico, antitussigeno, antiasmático e atividade expectorante do mirceno ou da nanoemulsão contendo mirceno. A NEMC foi formulada a partir do método de emulsificação espontânea, pela adição da fase aquosa, consistindo em solução tampão fosfato a uma fase orgânica, formada por óleo triglicerídeo de cadeia média, mirceno, agentes tensoativos em diferentes proporções, sob agitação constante e temperatura ambiente. O tamanho e o índice de polidispersão foram determinados. Este trabalho foi submetido ao Comitê de Ética no Uso de Animais da Universidade Federal do Vale do São Francisco (CEUA-UNIVASF), registrado com o Nº 0002/270121. A avaliação da toxicidade aguda pré-clínica foi realizada de acordo com o guia da OECD. Cada animal recebeu uma única dose de 2.000 mg/kg de NEMC por via oral, sendo observados nos primeiros 30, 60, 120, 180 e 360 min e a cada 24 h durante 14 dias. Para avaliação do comportamento motor e verificação do relaxamento muscular dos camundongos foram realizados os testes de campo aberto e rotarod. A avaliação da atividade espasmolítica em músculo liso de traqueia isolada de ratos foi realizada em banho de órgãos sob contrações induzidas por carbacol ou KCl. A atividade antitussígena foi avaliada pelo método de indução da tosse pelo ácido cítrico. A atividade antitussígena do mirceno administrado por via inalatória também foi avaliada. A avaliação da atividade expectorante foi realizada por meio do modelo de quantificação do vermelho de fenol. A atividade antiasmática foi avaliada pelo método de asma induzida por OVA. NEMC apresentou tamanho de 97,37 ± 5,844 nm e IPd de 0,2387 ± 0,01810. Testes de toxicidade aguda (2000 mg/kg, via oral) não apesentaram mortalidade nem alterações significativas em parâmetros fisiológicos. Em modelos experimentais, o β-mirceno (75 mg/kg) não afetou a coordenação motora (testes de campo aberto e rota-rod) e induziu relaxamento modesto (10,41 ± 5,11% sob contração por carbacol; 19,48 ± 5,12% por KCl) em traqueia isolada de rato. Na forma nanoemulsionada, a NEMC (75 mg/kg) reduziu significativamente a frequência de tosse induzida por ácido cítrico (55,62 ± 16,48% vs. 121,2 ± 9,41% do controle; p < 0,05), com mecanismo envolvendo vias GABAérgicas, opioides e canais de potássio. Ambas as formulações demonstraram atividade expectorante, aumentando a secreção de vermelho de fenol no lavado broncoalveolar (NEMC: 3,38 ± 0,29 µg/mL vs. 1,93 ± 0,11 µg/mL da salina). No modelo de asma por ovalbumina, a NEMC reduziu significativamente a migração de células inflamatórias, confirmando efeito antiasmático. Os resultados evidenciam que a nanoemulsão preserva as propriedades farmacológicas do β-mirceno, com vantagens na biodisponibilidade. Ambas as formulações exibiram efeitos antitussígenos, expectorantes e anti-inflamatórios, destacando seu potencial terapêutico para doenças respiratórias, particularmente asma e condições associadas. O estudo revela a nanoemulsão como estratégia promissora para veiculação de compostos lipofílicos.Submitted by Daniela Costa (dmscosta@uefs.br) on 2025-09-01T17:32:29Z No. of bitstreams: 1 BISMARQUES AUGUSTO OLIVEIRA DA SILVA - Tese.pdf: 1742043 bytes, checksum: c05ab13ec782adda65884b8492266aae (MD5)Made available in DSpace on 2025-09-01T17:32:29Z (GMT). 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dc.title.por.fl_str_mv Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
title Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
spellingShingle Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
Silva, Bismarques Augusto Oliveira da
Monoterpeno
Mirceno
Tosse
Expectoração
Asma
Nanotecnologia
Monoterpene
Myrcene
Expectoration
Asthma
Nanotechnology
OUTROS
title_short Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
title_full Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
title_fullStr Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
title_full_unstemmed Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
title_sort Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios
author Silva, Bismarques Augusto Oliveira da
author_facet Silva, Bismarques Augusto Oliveira da
author_role author
dc.contributor.advisor1.fl_str_mv Silva, Fabrício Souza
dc.contributor.advisor1ID.fl_str_mv https://orcid.org/0000-0002-6394-6501
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/7061608208191249
dc.contributor.authorID.fl_str_mv 1709626986626495
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/1709626986626495
dc.contributor.author.fl_str_mv Silva, Bismarques Augusto Oliveira da
contributor_str_mv Silva, Fabrício Souza
dc.subject.por.fl_str_mv Monoterpeno
Mirceno
Tosse
Expectoração
Asma
Nanotecnologia
topic Monoterpeno
Mirceno
Tosse
Expectoração
Asma
Nanotecnologia
Monoterpene
Myrcene
Expectoration
Asthma
Nanotechnology
OUTROS
dc.subject.eng.fl_str_mv Monoterpene
Myrcene
Expectoration
Asthma
Nanotechnology
dc.subject.cnpq.fl_str_mv OUTROS
description β-Myrcene is a monoterpene possessing anti-inflammatory, antioxidant, and antinociceptive properties. This study aimed to develop a myrcene-containing nanoemulsion (NEMC), evaluate its acute toxicity, and investigate the spasmolytic, antitussive, antiasthmatic, and expectorant effects of myrcene or the myrcene-containing nanoemulsion. NEMC was formulated using the spontaneous emulsification method. This involved adding an aqueous phase, consisting of a phosphate buffer solution, to an organic phase. The organic phase was composed of medium-chain triglyceride oil, myrcene, and surfactants in varying proportions, under constant stirring and at room temperature. The size and polydispersity index of the nanoemulsion were determined. This study was approved by the Ethics Committee on Animal Use of the Federal University of Vale do São Francisco (CEUA-UNIVASF), registered under No. 0002/270121. Preclinical acute toxicity was evaluated according to OECD guidelines. Each animal received a single oral dose of 2,000 mg/kg of NEMC and was observed at 30, 60, 120, 180, and 360 minutes, and every 24 hours for 14 days. Motor behavior and muscle relaxation in mice were assessed using open-field and rotarod tests. The spasmolytic activity on isolated rat tracheal smooth muscle was evaluated in an organ bath under carbachol or KCl-induced contractions. Antitussive activity was assessed using the citric acid-induced cough method. The antitussive activity of inhaled myrcene was also investigated. Expectorant activity was determined by quantifying phenol red. Antiasthmatic activity was evaluated using an ovalbumin (OVA)-induced asthma model. NEMC exhibited a size of 97.37±5.844 nm and a polydispersity index (PDI) of 0.2387±0.01810. Acute toxicity tests (2000 mg/kg, oral administration) showed no mortality or significant changes in physiological parameters. In experimental models, β-myrcene (75 mg/kg) did not affect motor coordination (open-field and rotarod tests) and induced modest relaxation (10.41±5.11% under carbachol contraction; 19.48±5.12% under KCl contraction) in isolated rat trachea. In its nanoemulsified form, NEMC (75 mg/kg) significantly reduced citric acid-induced cough frequency (55.62±16.48% vs. 121.2±9.41% of control; p < 0.05), with a mechanism involving GABAergic and opioid pathways, and potassium channels. Both formulations demonstrated expectorant activity, increasing phenol red secretion in bronchoalveolar lavage (NEMC: 3.38±0.29 µg/mL vs. 1.93±0.11 µg/mL for saline). In the ovalbumin-induced asthma model, NEMC significantly reduced the migration of inflammatory cells, confirming its antiasthmatic effect. These results indicate that the nanoemulsion preserves the pharmacological properties of β-myrcene, offering advantages in terms of bioavailability. Both formulations exhibited antitussive, expectorant, and anti-inflammatory effects, highlighting their therapeutic potential for respiratory diseases, particularly asthma and associated conditions. The study reveals the nanoemulsion as a promising strategy for delivering lipophilic compounds.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-09-01T17:32:29Z
dc.date.issued.fl_str_mv 2025-05-06
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv SILVA, Bismarques Augusto Oliveira da. Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios, 2025, 112 f., Tese (doutorado) - Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana.
dc.identifier.uri.fl_str_mv http://tede2.uefs.br:8080/handle/tede/1916
identifier_str_mv SILVA, Bismarques Augusto Oliveira da. Investigação farmacológica da nanoemulsão contendo β-Mirceno para o tratamento problemas respiratórios, 2025, 112 f., Tese (doutorado) - Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana.
url http://tede2.uefs.br:8080/handle/tede/1916
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv -5520924549352904568
dc.relation.confidence.fl_str_mv 600
600
600
600
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