Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part II: In vivo Efficacy Testing in a Rabbit Surfactant Washout Model.

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:
05 Sep 2024
Historique:
received: 29 05 2024
accepted: 26 07 2024
medline: 6 9 2024
pubmed: 6 9 2024
entrez: 5 9 2024
Statut: aheadofprint

Résumé

Surfactant therapy incorporates liquid bolus instillation via endotracheal tube catheter and a mechanical ventilator in preterm neonates with respiratory distress syndrome (RDS). Aerosolized surfactants have generated interest and conflicting data on the efficacy of phospholipid (PL) dose requirements. We developed and characterized a synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder aerosol product. In this study, we compare the in vivo performance of the new aerosol product with standard-of-care liquid instillation. Juvenile rabbits were sedated, anesthetized, intubated, and ventilated. Endogenous surfactant was depleted via whole lung lavage. Animals received either a standard dose of liquid Curosurf (200 mg PL/kg) instilled via a tracheal catheter, SLS-EEG powder aerosol (60 mg device loaded dose; equivalent to 24 mg PL/kg), or sham control. Gas exchange, lung compliance, and indices of disease severity were recorded every 30 min for 3.5 h and macro- and microscopy images were acquired at necropsy. While aerosol was administered at an approximately tenfold lower PL dose, both liquid-instilled and aerosol groups had similar, nearly complete recoveries of arterial oxygenation (PaO The new dry powder aerosol SLS product (which includes the delivery strategy, formulation, and delivery system) has the potential to be a safe, effective, and economical alternative to the current clinical standard of liquid bolus surfactant instillation.

Identifiants

pubmed: 39237797
doi: 10.1007/s11095-024-03754-7
pii: 10.1007/s11095-024-03754-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Bill and Melinda Gates Foundation
ID : INV-058340

Informations de copyright

© 2024. The Author(s).

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Auteurs

Robert M DiBlasi (RM)

Center for Respiratory Biology and Therapeutics, Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA, 98101, USA. robert.diblasi@seattlechildrens.org.

Hattie KenKnight (H)

Center for Respiratory Biology and Therapeutics, Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA, 98101, USA.

Niko Kontoudios (N)

Center for Respiratory Biology and Therapeutics, Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA, 98101, USA.

Dale Farkas (D)

Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA.

Mohammad A M Momin (MAM)

Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.

Felicia Hall (F)

Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.

Michael Hindle (M)

Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.

Worth Longest (W)

Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.
Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA.

Classifications MeSH