title: Biophysical inhibition of pulmonary surfactant function by polymeric nanoparticles: role of surfactant protein B and C.
abstract: The current study investigated the mechanisms involved in the process of biophysical inhibition of pulmonary surfactant by polymeric nanoparticles (NP). The minimal surface tension of diverse synthetic surfactants was monitored in the presence of bare and surface-decorated (i.e. poloxamer 407) sub-100 nm poly(lactide) NP. Moreover, the influence of NP on surfactant composition (i.e. surfactant protein (SP) content) was studied. Dose-elevations of SP advanced the biophysical activity of the tested surfactant preparation. Surfactant-associated protein C supplemented phospholipid mixtures (PLM-C) were shown to be more susceptible to biophysical inactivation by bare NP than phospholipid mixture supplemented with surfactant protein B (PLM-B) and PLM-B/C. Surfactant function was hindered owing to a drastic depletion of the SP content upon contact with bare NP. By contrast, surface-modified NP were capable of circumventing unwanted surfactant inhibition. Surfactant constitution influences the extent of biophysical inhibition by polymeric NP. Steric shielding of the NP surface minimizes unwanted NP-surfactant interactions, which represents an option for the development of surfactant-compatible nanomedicines.
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany. Electronic address: moritz.beck-broichsitter@innere.med.uni-giessen.de.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmehl
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
mesh_terms: D055592:Biophysical Phenomena; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D037701:Pulmonary Surfactant-Associated Protein B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D010743:Phospholipids; D011091:Polyesters; D011108:Polymers; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Biophysical inhibition; Hydrophobic surfactant proteins; Polymeric nanoparticles; Pulmonary drug delivery; Pulmonary surfactant