title: Nebulizing poractant alfa versus conventional instillation: Ultrastructural appearance and preservation of surface activity.
abstract: BACKGROUND
  Nebulized surfactant therapy has been proposed as an alternative method of surfactant administration. The use of a perforated vibrating membrane nebulizer provides a variety of advantages over conventional nebulizers. We investigated the molecular structure and integrity of poractant alfa pre- and post-nebulization.
  
  
  METHODS
  Curosurf® was nebulized using an Investigational eFlow® Nebulizer System. Non-nebulized surfactant ("NN"), recollected surfactant droplets from nebulization through an endotracheal tube ("NT") and nebulization of surfactant directly onto a surface ("ND") were investigated by transmission electron microscopy. Biophysical characteristics were assessed by the Langmuir-Wilhelmy balance and the Captive Bubble Surfactometer.
  
  
  RESULTS
  Volume densities of lamellar body-like forms (LBL) and multi-lamellar forms (ML) were high for "NN" and "NT" samples (38.8% vs. 47.7% for LBL and 58.2% vs. 47.8% for ML). In the "ND" sample, we found virtually no LBL's, ML's (72.6%) as well as uni-lamellar forms (16.4%) and a new structure, the "garland-like" forms (9.4%). Surface tension for "NN" and "NT" was 23.33 ± 0.29 and 25.77 ± 1.12 mN/m, respectively. Dynamic compression-expansion cycling minimum surface tensions were between 0.91 and 1.77 mN/m.
  
  
  CONCLUSIONS
  The similarity of surfactant characteristics of nebulized surfactant via a tube and the non-nebulized surfactant suggests that vibrating membrane nebulizers are suitable for surfactant nebulization. Alterations in surfactant morphology and characteristics after nebulization were transient. A new structural subtype of surfactant was identified.
authors.affiliation: The University of Western Australia, Centre for Neonatal Research and Education, Perth, Australia; Department of Neonatology and Intensive Care, University Children's Hospital, Zurich, Switzerland; Department of Pediatrics, University Hospital Bern, Bern, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Minocchieri
authors.forename: Stephan
authors.initials: S
authors.lastname: Knoch
authors.forename: W Michael
authors.initials: WM
authors.lastname: Schoel
authors.forename: Matthias
authors.initials: M
authors.lastname: Ochs
authors.forename: Mathias
authors.initials: M
authors.lastname: Nelle
mesh_terms: D001688:Biological Products / Q000008:administration & dosage*; D007322:Instillation, Drug; D046529:Microscopy, Electron, Transmission; D009330:Nebulizers and Vaporizers; D010743:Phospholipids / Q000008:administration & dosage*; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D013500:Surface Tension
chemical_list: D001688:Biological Products; D010743:Phospholipids; D011663:Pulmonary Surfactants; C068291:poractant alfa
keywords: aerosol drug therapy; nebulizer; neonatal respiratory distress syndrome; pulmonary surfactant; surface tension