Synthetic lung surfactants containing SP-B and SP-C peptides plus novel phospholipase-resistant lipids or glycerophospholipids

• Published in: PeerJ (San Francisco, CA) CA), 2016-10, Vol.4, p.e2635-e2635, Article e2635
• Main Authors: Notter, Robert H, Gupta, Rohun, Schwan, Adrian L, Wang, Zhengdong, Shkoor, Mohanad Gh, Walther, Frans J
• Format: Article
• Language: English
• Subjects: Adsorption; Adults; Bioengineering; Biomedical research; Biophysics; Compression; DEPN-8; Fatty acids; Health aspects; Lecithin; Lipids; Lung diseases; Lungs; Mortality; Oxygenation; Pediatrics; Peptides; Phosphatidylcholine; Phosphatidylglycerol; Phospholipase; Phospholipase-resistant lung surfactants; Phospholipases; Phospholipids; Phosphonolipids; Physiology; Proteins; Respiratory distress syndrome; Respiratory function; Respiratory Medicine; SP-B and SP-C peptide mimics; SP-Css ion-lock 1; Super Mini-B DATK; Surface active agents; Surface activity; Surfactant protein B (SP-B); Surfactants; Synthetic Biology; Therapeutic applications; Viscosity
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.2635

This study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB) DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP)-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl-oleoyl phosphatidylglycerol (POPG), while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight). The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary) for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury. Surface activity of synthetic lipid/peptide surfactants was assessed at 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer. pulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance) in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO to