α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

Ana Paula L D’Almeida,1,* Maria T Pacheco de Oliveira,1,* Éverton T de Souza,1 Diego de Sá Coutinho,1 Bianca T Ciambarella,1 Cristiano R Gomes,1 Thatiana Terroso,2 Sílvia S Guterres,2 Adriana R Pohlmann,3 Patrícia MR Silva,1 Marco A Martins,1 And...

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Autores principales: D’Almeida APL, Pacheco de Oliveira MT, de Souza ÉT, de Sá Coutinho D, Ciambarella BT, Gomes CR, Terroso T, Guterres SS, Pohlmann AR, Silva PMR, Martins MA, Bernardi A
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:d8aaa62bd7a54dd4af707ec5477316372021-12-02T02:16:50Zα-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice1178-2013https://doaj.org/article/d8aaa62bd7a54dd4af707ec5477316372017-06-01T00:00:00Zhttps://www.dovepress.com/alpha-bisabolol-loaded-lipid-core-nanocapsules-reduce-lipopolysacchari-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ana Paula L D’Almeida,1,* Maria T Pacheco de Oliveira,1,* Éverton T de Souza,1 Diego de Sá Coutinho,1 Bianca T Ciambarella,1 Cristiano R Gomes,1 Thatiana Terroso,2 Sílvia S Guterres,2 Adriana R Pohlmann,3 Patrícia MR Silva,1 Marco A Martins,1 Andressa Bernardi1 1Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Pharmaceutical Sciences Post-Graduation Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; 3Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil *These authors contributed equally to this work Abstract: Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs. α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application. This study was conducted to develop a drug delivery system using lipid-core nanocapsules (LNCs) to improve the anti-inflammatory effects of orally administered α-bis. α-bis-loaded LNCs (α-bis-LNCs) were prepared by interfacial deposition of poly(ε-caprolactone) and orally administered in a mouse model of ARDS triggered by an intranasal administration of lipopolysaccharide (LPS). We found that α-bis-LNCs (30, 50, and 100 mg kg-1) significantly reduced airway hyperreactivity (AHR), neutrophil infiltration, myeloperoxidase activity, chemokine levels (KC and MIP-2), and tissue lung injury 18 hours after the LPS challenge. By contrast, free α-bis failed to modify AHR and neutrophil accumulation in the bronchoalveolar lavage effluent and lung parenchyma and inhibited elevation in the myeloperoxidase and MIP-2 levels only at the highest dose. Furthermore, only α-bis-LNCs reduced LPS-induced changes in mitogen-activated protein kinase signaling, as observed by a significant reduction in phosphorylation levels of ERK1/2, JNK, and p38 proteins. Taken together, our results clearly show that by using LNCs, α-bis was able to decrease LPS-induced inflammation. These findings may be explained by the robust increase of α-bis concentration in the lung tissue that was achieved by the LNCs. Altogether, these results indicate that α-bis-LNCs should further be investigated as a potential alternative for the treatment of ARDS. Keywords: acute respiratory distress syndrome, nanotechnology, drug delivery, pulmonary inflammation, α-bisabolol, anti-inflammatory effectsD’Almeida APLPacheco de Oliveira MTde Souza ÉTde Sá Coutinho DCiambarella BTGomes CRTerroso TGuterres SSPohlmann ARSilva PMRMartins MABernardi ADove Medical Pressarticleacute respiratory distress syndromenanotechnologydrug deliverypulmonary inflammationα-bisabololanti-inflammatory effects.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4479-4491 (2017)
institution DOAJ
collection DOAJ
language EN
topic acute respiratory distress syndrome
nanotechnology
drug delivery
pulmonary inflammation
α-bisabolol
anti-inflammatory effects.
Medicine (General)
R5-920
spellingShingle acute respiratory distress syndrome
nanotechnology
drug delivery
pulmonary inflammation
α-bisabolol
anti-inflammatory effects.
Medicine (General)
R5-920
D’Almeida APL
Pacheco de Oliveira MT
de Souza ÉT
de Sá Coutinho D
Ciambarella BT
Gomes CR
Terroso T
Guterres SS
Pohlmann AR
Silva PMR
Martins MA
Bernardi A
α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice
description Ana Paula L D’Almeida,1,* Maria T Pacheco de Oliveira,1,* Éverton T de Souza,1 Diego de Sá Coutinho,1 Bianca T Ciambarella,1 Cristiano R Gomes,1 Thatiana Terroso,2 Sílvia S Guterres,2 Adriana R Pohlmann,3 Patrícia MR Silva,1 Marco A Martins,1 Andressa Bernardi1 1Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Pharmaceutical Sciences Post-Graduation Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; 3Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil *These authors contributed equally to this work Abstract: Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs. α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application. This study was conducted to develop a drug delivery system using lipid-core nanocapsules (LNCs) to improve the anti-inflammatory effects of orally administered α-bis. α-bis-loaded LNCs (α-bis-LNCs) were prepared by interfacial deposition of poly(ε-caprolactone) and orally administered in a mouse model of ARDS triggered by an intranasal administration of lipopolysaccharide (LPS). We found that α-bis-LNCs (30, 50, and 100 mg kg-1) significantly reduced airway hyperreactivity (AHR), neutrophil infiltration, myeloperoxidase activity, chemokine levels (KC and MIP-2), and tissue lung injury 18 hours after the LPS challenge. By contrast, free α-bis failed to modify AHR and neutrophil accumulation in the bronchoalveolar lavage effluent and lung parenchyma and inhibited elevation in the myeloperoxidase and MIP-2 levels only at the highest dose. Furthermore, only α-bis-LNCs reduced LPS-induced changes in mitogen-activated protein kinase signaling, as observed by a significant reduction in phosphorylation levels of ERK1/2, JNK, and p38 proteins. Taken together, our results clearly show that by using LNCs, α-bis was able to decrease LPS-induced inflammation. These findings may be explained by the robust increase of α-bis concentration in the lung tissue that was achieved by the LNCs. Altogether, these results indicate that α-bis-LNCs should further be investigated as a potential alternative for the treatment of ARDS. Keywords: acute respiratory distress syndrome, nanotechnology, drug delivery, pulmonary inflammation, α-bisabolol, anti-inflammatory effects
format article
author D’Almeida APL
Pacheco de Oliveira MT
de Souza ÉT
de Sá Coutinho D
Ciambarella BT
Gomes CR
Terroso T
Guterres SS
Pohlmann AR
Silva PMR
Martins MA
Bernardi A
author_facet D’Almeida APL
Pacheco de Oliveira MT
de Souza ÉT
de Sá Coutinho D
Ciambarella BT
Gomes CR
Terroso T
Guterres SS
Pohlmann AR
Silva PMR
Martins MA
Bernardi A
author_sort D’Almeida APL
title α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice
title_short α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice
title_full α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice
title_fullStr α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice
title_full_unstemmed α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice
title_sort α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/d8aaa62bd7a54dd4af707ec547731637
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