Aerosol, chemical and physical properties of dry powder synthetic lung surfactant for noninvasive treatment of neonatal respiratory distress syndrome

• Published in: Scientific reports 2021-08, Vol.11 (1), p.16439-10, Article 16439
• Main Authors: Walther, Frans J., Chan, Holly, Smith, Jacob R., Tauber, Mike, Waring, Alan J.
• Format: Article
• Language: English
• Subjects: 631/45; 631/57; 631/61; 692/308; Aerosols - chemistry; Amino Acid Sequence; Continuous positive airway pressure; Drying; Humanities and Social Sciences; Humans; Infant, Newborn; Infant, Premature; Infants; Inhalation; Lactose; multidisciplinary; Neonates; Peptides; Phospholipids; Physical properties; Powder; Powders - chemistry; Premature babies; Premature birth; Protein B; Pulmonary Surfactants - chemistry; Pulmonary Surfactants - therapeutic use; Respiratory distress syndrome; Respiratory Distress Syndrome, Newborn - drug therapy; Science; Science (multidisciplinary); Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface activity; Surfactants; Trehalose
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-95999-0

Inhalation of dry powder synthetic lung surfactant may assist spontaneous breathing by providing noninvasive surfactant therapy for premature infants supported with nasal continuous positive airway pressure. Surfactant was formulated using spray-drying with different phospholipid compositions (70 or 80 total weight% and 7:3 or 4:1 DPPC:POPG ratios), a surfactant protein B peptide analog (KL4, Super Mini-B, or B-YL), and Lactose or Trehalose as excipient. KL4 surfactant underperformed on initial adsorption and surface activity at captive bubble surfactometry. Spray-drying had no effect on the chemical composition of Super Mini-B and B-YL peptides and surfactant with these peptides had excellent surface activity with particle sizes and fine particle fractions that were well within the margins for respiratory particles and similar solid-state properties. Prolonged exposure of the dry powder surfactants with lactose as excipient to 40 °C and 75% humidity negatively affected hysteresis during dynamic cycling in the captive bubble surfactometer. Dry powder synthetic lung surfactants with 70% phospholipids (DPPC and POPG at a 7:3 ratio), 25% trehalose and 3% of SMB or B-YL showed excellent surface activity and good short-term stability, thereby qualifying them for potential clinical use in premature infants.