Exogenous Surfactant as a Pulmonary Drug Delivery Vehicle for Budesonide in the Treatment of ARDS
Notice bibliographique
Résumé
Background Inflammation associated with diseases like Acute Respiratory Distress Syndrome (ARDS) and Bacterial Pneumonia, often occurs in the deeper, alveolar, areas of the lung. In these circumstances the complex branching structure of the lung, its large surface area, and associated areas of airway collapse provide substantial hurdles for adequate delivery of anti‐inflammatory drugs to remote regions of inflammation. To address this, our lab has utilized a bovine derived exogenous surfactant (BLES) as a pulmonary vehicle to facilitate the transport of a glucocorticoid (budesonide). Budesonide is a strong anti‐inflammatory drug currently used in the lung to treat asthma, while BLES can open collapsed airways and spread to distal sites within the lung. Hypothesis Combining budesonide with a bovine derived exogenous surfactant will enhance its delivery and efficacy for treating pulmonary inflammation. Methods Our hypothesis was tested using both in vitro and in vivo methodology. For in vitro studies the wet bridge transfer system was utilized to assess spreading and efficacy of budesonide alone or in combination with BLES across an air‐liquid interface. In this system, macrophages were seeded to a remote site and stimulated with heat‐killed bacteria (HKB). Treatments were then administered to a delivery site and IL‐6 concentrations were measured at the remote site. An in vivo model of pulmonary inflammation was created by instilling either saline (control) or HKB into the lungs of male and female rats. This first instillation was followed 30 minutes later by a second instillation of either saline, budesonide or BLES/budesonide. Rats were then monitored for six hours before being euthanized. A bronchoalveolar lavage (BAL) was performed, followed by cell counts and differentials. Results The in vitro data showed that administering BLES or budesonide alone had no effect on IL‐6 concentrations at the remote site, across the air‐liquid interface. However, the administration of BLES/budesonide significantly reduced IL‐6 content at the remote site. Data collected from the in vivo experiment indicates that instillation of HKB significantly increased the number of inflammatory cells and neutrophils in the BAL compared to the control. Budesonide alone was able to show a reduction in the number of neutrophils in the BAL. However, BLES/budesonide showed significant reductions in both the number of inflammatory cells and neutrophils in the BAL compared to budesonide and HKB groups. Discussion The in vitro data indicates that BLES/budesonide is more effective at reaching and eliciting an anti‐inflammatory effect at a distal site than budesonide alone. Moreover, administering budesonide with BLES in vivo resulted in significant improvements in drug delivery and efficacy. Further measurements of pulmonary inflammation will include myeloperoxidase assays as well as quantifying pro‐inflammatory cytokine mRNA and protein through qPCR and ELISA assays respectively. This novel strategy of utilizing a spreading agent to delivery budesonide represents a new therapy for pulmonary inflammation and a novel approach for directly delivering drugs to distal regions in the lung of ARDS patients. Support or Funding Information Ontario Graduate Scholarship ‐ Doctoral
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».