Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part I: In Vitro Testing and Characterization.
infant aerosol therapy
respiratory distress syndrome
surfactant aerosol
surfactant replacement therapy
synthetic lung surfactant
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
07 Aug 2024
07 Aug 2024
Historique:
received:
24
05
2024
accepted:
03
07
2024
medline:
8
8
2024
pubmed:
8
8
2024
entrez:
7
8
2024
Statut:
aheadofprint
Résumé
Improving the deep lung delivery of aerosol surfactant therapy (AST) with a dry powder formulation may enable significant reductions in dose while providing improved efficacy. The objective of Part I of this two-part study was to present the development of a new dry powder aerosol synthetic lung surfactant (SLS) product and to characterize performance based on aerosol formation and realistic in vitro airway testing leading to aerosol delivery recommendations for subsequent in vivo animal model experiments. A new micrometer-sized SLS excipient enhanced growth (EEG) dry powder formulation was produced via spray drying and aerosolized using a positive-pressure air-jet dry powder inhaler (DPI) intended for aerosol delivery directly to intubated infants with respiratory distress syndrome (RDS) or infant-size test animals. The best-case design (D2) of the air-jet DPI was capable of high emitted dose (> 80% of loaded) and formed a < 2 µm mass median aerodynamic diameter (MMAD) aerosol, but was limited to ≤ 20 mg mass loadings. Testing with a realistic in vitro rabbit model indicated that over half of the loaded dose could penetrate into the lower lung regions. Using the characterization data, a dose delivery protocol was designed in which a 60 mg total loaded dose would be administered and deliver an approximate lung dose of 14.7-17.7 mg phospholipids/kg with a total aerosol delivery period < 5 min. A high-efficiency aerosol SLS product was designed and tested that may enable an order of magnitude reduction in administered phospholipid dose, and provide rapid aerosol administration to infants with RDS.
Identifiants
pubmed: 39112775
doi: 10.1007/s11095-024-03740-z
pii: 10.1007/s11095-024-03740-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : HL139673
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL139673
Pays : United States
Organisme : Bill and Melinda Gates Foundation
ID : INV-055026
Organisme : Bill and Melinda Gates Foundation
ID : INV-058340
Informations de copyright
© 2024. The Author(s).
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