Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo.
Drug delivery
Exogenous surfactant
Glucocorticoids
Pulmonary inflammation
Journal
Lung
ISSN: 1432-1750
Titre abrégé: Lung
Pays: United States
ID NLM: 7701875
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
24
07
2020
accepted:
14
10
2020
pubmed:
28
10
2020
medline:
8
10
2021
entrez:
27
10
2020
Statut:
ppublish
Résumé
Lung inflammation is associated with many respiratory conditions. Consequently, anti-inflammatory medications, like glucocorticoids, have become mainstay intrapulmonary therapeutics. However, their effectiveness for treating inflammation occurring in the alveolar regions of the lung is limited by suboptimal delivery. To improve the pulmonary distribution of glucocorticoids, such as budesonide to distal regions of the lung, exogenous surfactant has been proposed as an ideal delivery vehicle for such therapies. It was therefore hypothesized that fortifying an exogenous surfactant (BLES) with budesonide would enhance efficacy for treating pulmonary inflammation in vivo. An intratracheal instillation of heat-killed bacteria was used to elicit an inflammatory response in the lungs of male and female rats. Thirty minutes after this initial instillation, either budesonide or BLES combined with budesonide was administered intratracheally. To evaluate the efficacy of surfactant delivery, various markers of inflammation were measured in the bronchoalveolar lavage and lung tissue. Although budesonide exhibited anti-inflammatory effects when administered alone, delivery with BLES enhanced those effects by lowering the lavage neutrophil counts and myeloperoxidase activity in lung tissue. Combining budesonide with BLES was also shown to reduce several other pro-inflammatory mediators. These results were shown across both sexes, with no observed sex differences. Based on these findings, it was concluded that exogenous surfactant can enhance the delivery and efficacy of budesonide in vivo.
Sections du résumé
BACKGROUND
Lung inflammation is associated with many respiratory conditions. Consequently, anti-inflammatory medications, like glucocorticoids, have become mainstay intrapulmonary therapeutics. However, their effectiveness for treating inflammation occurring in the alveolar regions of the lung is limited by suboptimal delivery. To improve the pulmonary distribution of glucocorticoids, such as budesonide to distal regions of the lung, exogenous surfactant has been proposed as an ideal delivery vehicle for such therapies. It was therefore hypothesized that fortifying an exogenous surfactant (BLES) with budesonide would enhance efficacy for treating pulmonary inflammation in vivo.
METHODS
An intratracheal instillation of heat-killed bacteria was used to elicit an inflammatory response in the lungs of male and female rats. Thirty minutes after this initial instillation, either budesonide or BLES combined with budesonide was administered intratracheally. To evaluate the efficacy of surfactant delivery, various markers of inflammation were measured in the bronchoalveolar lavage and lung tissue.
RESULTS
Although budesonide exhibited anti-inflammatory effects when administered alone, delivery with BLES enhanced those effects by lowering the lavage neutrophil counts and myeloperoxidase activity in lung tissue. Combining budesonide with BLES was also shown to reduce several other pro-inflammatory mediators. These results were shown across both sexes, with no observed sex differences.
CONCLUSION
Based on these findings, it was concluded that exogenous surfactant can enhance the delivery and efficacy of budesonide in vivo.
Identifiants
pubmed: 33106891
doi: 10.1007/s00408-020-00399-2
pii: 10.1007/s00408-020-00399-2
pmc: PMC7587541
doi:
Substances chimiques
Biological Products
0
Glucocorticoids
0
Pharmaceutical Vehicles
0
Pulmonary Surfactants
0
Budesonide
51333-22-3
calfactant
Q4K217VGA9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
909-916Subventions
Organisme : Government of Ontario
ID : Ontario Graduate Scholarship (OGS)
Pays : International
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