In Vitro Functional and Structural Characterization of A Synthetic Clinical Pulmonary Surfactant with Enhanced Resistance to Inhibition.
Animals
Biological Products
/ chemistry
Blood Proteins
/ chemistry
Drug Delivery Systems
Humans
Peptide Fragments
/ antagonists & inhibitors
Phosphatidylcholines
/ antagonists & inhibitors
Phosphatidylglycerols
/ chemistry
Phospholipids
/ chemistry
Pulmonary Surfactant-Associated Protein B
/ antagonists & inhibitors
Pulmonary Surfactant-Associated Protein C
/ antagonists & inhibitors
Pulmonary Surfactants
/ antagonists & inhibitors
Structure-Activity Relationship
Surface Tension
Swine
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 Jan 2020
28 Jan 2020
Historique:
received:
18
10
2019
accepted:
13
01
2020
entrez:
30
1
2020
pubmed:
30
1
2020
medline:
3
6
2020
Statut:
epublish
Résumé
CHF5633 is a novel synthetic clinical pulmonary surfactant preparation composed by two phospholipid species, dipalmitoyl phosphatidylcholine (DPPC) and palmitoyloleoyl phosphatidylglycerol (POPG), and synthetic analogues of the hydrophobic surfactant proteins SP-B and SP-C. In this study, the interfacial properties of CHF5633 in the absence and in the presence of inhibitory serum proteins have been assessed in comparison with a native surfactant purified from porcine lungs and with poractant alpha, a widely used clinical surfactant preparation. The study of the spreading properties of CHF5633 in a Wilhelmy balance, its ability to adsorb and accumulate at air-liquid interfaces as revealed by a multiwell fluorescence assay, and its dynamic behavior under breathing-like compression-expansion cycling in a Captive Bubble Surfactometer (CBS), all revealed that CHF5633 exhibits a good behavior to reduce and sustain surface tensions to values below 5 mN/m. CHF5633 shows somehow slower initial interfacial adsorption than native surfactant or poractant alpha, but a better resistance to inhibition by serum proteins than the animal-derived clinical surfactant, comparable to that of the full native surfactant complex. Interfacial CHF5633 films formed in a Langmuir-Blodgett balance coupled with epifluorescence microscopy revealed similar propensity to segregate condensed lipid domains under compression than films made by native porcine surfactant or poractant alpha. This ability of CHF5633 to segregate condensed lipid phases can be related with a marked thermotropic transition from ordered to disordered membrane phases as exhibited by differential scanning calorimetry (DSC) of CHF5633 suspensions, occurring at similar temperatures but with higher associated enthalpy than that shown by poractant alpha. The good interfacial behavior of CHF5633 tested under physiologically meaningful conditions in vitro and its higher resistance to inactivation by serum proteins, together with its standardized and well-defined composition, makes it a particularly useful therapeutic preparation to be applied in situations associated with lung inflammation and edema, alone or in combined strategies to exploit surfactant-facilitated drug delivery.
Identifiants
pubmed: 31992800
doi: 10.1038/s41598-020-58248-4
pii: 10.1038/s41598-020-58248-4
pmc: PMC6987218
doi:
Substances chimiques
Biological Products
0
Blood Proteins
0
CHF5633
0
Peptide Fragments
0
Phosphatidylcholines
0
Phosphatidylglycerols
0
Phospholipids
0
Pulmonary Surfactant-Associated Protein B
0
Pulmonary Surfactant-Associated Protein C
0
Pulmonary Surfactants
0
1-palmitoyl-2-oleoylglycero-3-phosphoglycerol
81490-05-3
poractant alfa
KE3U2023NP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1385Références
King, R. J. & Clements, J. A. Surface active materials from dog lung. II. Composition and physiological correlations. Am. J. Physiol. 223, 715–26 (1972).
doi: 10.1152/ajplegacy.1972.223.3.715
Perez-Gil, J. & Weaver, T. E. Pulmonary surfactant pathophysiology: current models and open questions. Physiology (Bethesda). 25, 132–41 (2010).
pubmed: 20551227
Singh, N., et al. Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev, Cd010249 (2015).
Cavicchioli, P. et al. Endogenous surfactant turnover in preterm infants with respiratory distress syndrome studied with stable isotope lipids. Am J Respir Crit Care Med. 163, 55–60 (2001).
doi: 10.1164/ajrccm.163.1.2005029
Blanco, O. & Perez-Gil, J. Biochemical and pharmacological differences between preparations of exogenous natural surfactant used to treat Respiratory Distress Syndrome: role of the different components in an efficient pulmonary surfactant. Eur J Pharmacol. 568, 1–15 (2016).
doi: 10.1016/j.ejphar.2007.04.035
Dushianthan, A., Cusack, R., Goss, V., Postle, A. D. & Grocott, M. P. Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome–where do we go from here? Crit Care. 16, 238 (2012).
doi: 10.1186/cc11512
Echaide, M., Autilio, C., Arroyo, R. & Perez-Gil, J. Restoring pulmonary surfactant membranes and films at the respiratory surface. Biochim Biophys Acta Biomembr. 1859, 1725–39 (2017).
doi: 10.1016/j.bbamem.2017.03.015
Sweet, D. et al. A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome. Arch Dis Child Fetal Neonatal. 102, F497–503 (2017).
doi: 10.1136/archdischild-2017-312722
Sato, A. & Ikegami, M. SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung. PLoS One. 7, e39392 (2012).
doi: 10.1371/journal.pone.0039392
Glaser, K. et al. The new generation synthetic reconstituted surfactant CHF5633 suppresses LPS-induced cytokine responses in human neonatal monocytes. Cytokine. 86, 119–23 (2016).
doi: 10.1016/j.cyto.2016.08.004
Mingarro, I., Lukovic, D., Vilar, M. & Perez-Gil, J. Synthetic pulmonary surfactant preparations: new developments and future trends. Curr Med Chem. 15, 393–403 (2008).
doi: 10.2174/092986708783497364
Almlen, A. et al. Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits. Neonatology. 98, 91–9 (2010).
doi: 10.1159/000276980
Taeusch, H. W., Bernardino de la Serna, J., Perez-Gil, J., Alonso, C. & Zasadzinski, J. A. Inactivation of pulmonary surfactant due to serum-inhibited adsorption and reversal by hydrophilic polymers: experimental. Biophys J. 89, 1769–79 (2005).
doi: 10.1529/biophysj.105.062620
Lopez-Rodriguez, E., Ospina, O. L., Echaide, M., Taeusch, H. W. & Perez-Gil, J. Exposure to polymers reverses inhibition of pulmonary surfactant by serum, meconium, or cholesterol in the captive bubble surfactometer. Biophys J. 103, 1451–9 (2012).
doi: 10.1016/j.bpj.2012.08.024
Seehase, M. et al. New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs. PLoS One. 7, e47631 (2012).
doi: 10.1371/journal.pone.0047631
Cerrada, A., Haller, T., Cruz, A. & Pérez-Gil, J. Pneumocytes Assemble Lung Surfactant as Highly Packed/Dehydrated States with Optimal Surface Activity. Biophys J. 11, 2295–306 (2015).
doi: 10.1016/j.bpj.2015.10.022
Bernardino de la Serna, J. et al. Segregated phases in pulmonary surfactant membranes do not show coexistence of lipid populations with differentiated dynamic properties. Biophys J. 97, 1381–9 (2009).
doi: 10.1016/j.bpj.2009.06.040
Serrano, A. G. & Perez-Gil, J. Protein-lipid interactions and surface activity in the pulmonary surfactant system. Chem Phys Lipids. 141, 105–18 (2006).
doi: 10.1016/j.chemphyslip.2006.02.017
Lopez-Rodriguez, E., Pascual, A., Arroyo, R., Floros, J. & Perez-Gil, J. Human Pulmonary Surfactant Protein SP-A1 Provides Maximal Efficiency of Lung Interfacial Films. Biophys J. 111, 524–36 (2016).
doi: 10.1016/j.bpj.2016.06.025
Ricci, F., Murgia, W., Razzetti, R., Pelizzi, N. & Salomone, F. In vitro and in vivo comparison between poractant alfa and the new generation ynthetic surfactant CHF5633. Pediatric Research. 81(2), 369–375 (2017).
doi: 10.1038/pr.2016.231
Wang, L., Cruz, A., Flach, C. R., Perez-Gil, J. & Mendelsohn, R. Langmuir-Blodgett films formed by continuously varying surface pressure. Characterization by IR spectroscopy and epifluorescence microscopy. Langmuir. 23, 4950–8 (2007).
doi: 10.1021/la063139h
Plasencia, I., Keough, K. M. & Perez-Gil, J. Interaction of the N-terminal segment of pulmonary surfactant protein SP-C with interfacial phospholipid films. Biochim Biophys Acta. 1713, 118–28 (2005).
doi: 10.1016/j.bbamem.2005.06.002
Cruz, A. et al. Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers. Eur Biophys. 29, 204–13 (2000).
doi: 10.1007/PL00006647
Autilio, C. & Perez-Gil, J. Understanding the principle biophysics concepts of pulmonary surfactant in health and disease. Arch Dis Child Fetal Neonatal Ed. 104, F443–F451 (2019).
pubmed: 30552091
Casals, C. et al. Increase of C-reactive protein and decrease of surfactant protein A in surfactant after lung transplantation. Am J Respir Crit Care Med. 157, 43–9 (1998).
doi: 10.1164/ajrccm.157.1.9611106
Saenz, A. et al. Fluidizing effects of C-reactive protein on lung surfactant membranes: protective role of surfactant protein A. FASEB J. 24, 3662–73 (2010).
doi: 10.1096/fj.09-142646
De Luca, D., Capoluongo, E. & Rigo, V. Study group on Secretory Phospholipase in P. Secretory phospholipase A2 pathway in various types of lung injury in neonates and infants: a multicentre translational study. BMC Pediatr. 11, 101 (2011).
doi: 10.1186/1471-2431-11-101
Lugones, Y. et al. Inhibition and counterinhibition of Surfacen, a clinical lung surfactant of natural origin. PLoS One. 13, e0204050 (2018).
doi: 10.1371/journal.pone.0204050
Williams, I., Zasadzinski, J. & Squires, T. Interfacial rheology and direct imaging reveal domain-templated network formation in phospholipid monolayers penetrated by fibrinogen. Soft Matter. 15, 9076–9084 (2019).
doi: 10.1039/C9SM01519A
Johansson, J. & Curstedt, T. Synthetic surfactants with SP-B and SP-C analogues to enable worldwide treatment of neonatal respiratory distress syndrome and other lung diseases. J Intern Med. 285, 165–186 (2019).
doi: 10.1111/joim.12845
Rouser, G., Siakotos, A. N. & Fleischer, S. Quantitative analysis of phospholipids by thin-layer chromatography and phosphorus analysis of spots. Lipids. 1, 85–6 (1966).
doi: 10.1007/BF02668129
Schurch, D., Ospina, O. L., Cruz, A. & Perez-Gil, J. Combined and independent action of proteins SP-B and SP-C in the surface behavior and mechanical stability of pulmonary surfactant films. Biophys J. 99, 3290–9 (2010).
doi: 10.1016/j.bpj.2010.09.039
Hobi, N. et al. Physiological variables affecting surface film formation by native lamellar body-like pulmonary surfactant particles. Biochim Biophys Acta. 7, 1842–50 (2014).
doi: 10.1016/j.bbamem.2014.02.015
Ravasio, A., Cruz, A., Perez-Gil, J. & Haller, T. High-throughput evaluation of pulmonary surfactant adsorption and surface film formation. J Lipid Res. 49, 2479–88 (2008).
doi: 10.1194/jlr.D800029-JLR200