Synthetic mimics of surfactant proteins B and C: in vitro surface activity and effects on lung compliance in two animal models of surfactant deficiency.
Synthetic surfactant peptides SP-B1-78 and SP-C1-31 in a standard phospholipid mixture have been employed to examine the correlation between in vitro surface activity and in vivo function of synthetic surfactant preparations in the isolated rat lung and premature rabbit models of respiratory distress syndrome. Monolayer techniques showed that SP-B peptides have a high propensity for association with a phospholipid structure. By dynamic respreading, synthetic SP-B and SP-C showed rapid spreading and attained low surface tensions. Used as replacement surfactants in two animal models, these synthetic surfactant preparations partially restored lung compliance in lavaged rats and premature rabbits better than a pure phospholipid preparation and to a degree comparable to clinical surfactant, measured by pressure/volume curves. Our data confirm that in vitro functional determinations of synthetic surfactant peptides are instrumental in the preparation of replacement surfactants, and that dispersions thus selected represent viable therapeutic alternatives to current treatments for respiratory distress syndrome.
Bruni
R
R
Department of Pediatrics, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA.
Hernández-Juviel
J M
JM
Tanoviceanu
R
R
Walther
F J
FJ
D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs; D004304:Dosage Forms; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008055:Lipids / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects*; D008170:Lung Compliance / Q000187:drug effects; D008969:Molecular Sequence Data; D007752:Obstetric Labor, Premature / Q000662:veterinary; D011247:Pregnancy; D011510:Proteolipids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy*; D013500:Surface Tension / Q000187:drug effects
D004304:Dosage Forms; D008055:Lipids; D011510:Proteolipids; D011663:Pulmonary Surfactants