title: Biophysical inhibition of synthetic vs. naturally-derived pulmonary surfactant preparations by polymeric nanoparticles.
abstract: Reasonable suspicion has accumulated that inhaled nano-scale particulate matter influences the biophysical function of the pulmonary surfactant system. Hence, it is evident to provide novel insights into the extent and mechanisms of nanoparticle-surfactant interactions in order to facilitate the fabrication of safe nanomedicines suitable for pulmonary applications. Negatively- and positively-charged poly(styrene) nanoparticles (diameters of ~100nm) served as model carriers. Nanoparticles were incubated with several synthetic and naturally-derived pulmonary surfactants to characterize the sensitivity of each preparation to biophysical inactivation. Changes in surface properties (i.e. adsorption and dynamic surface tension behavior) were monitored in a pulsating bubble surfactometer. Both nanoparticle formulations revealed a dose-dependent influence on the biophysical behavior of all investigated pulmonary surfactants. However, the surfactant sensitivity towards inhibition depended on both the carrier type, where negatively-charged nanoparticles showed increased inactivation potency compared to their positively-charged counterparts, and surfactant composition. Among the surfactants tested, synthetic mixtures (i.e. phospholipids, phospholipids supplemented with surfactant protein B, and Venticute®) were more susceptible to surface-activity inhibition as the more complex naturally-derived preparations (i.e. Alveofact® and large surfactant aggregates isolated from rabbit bronchoalveolar lavage fluid). Overall, nanoparticle characteristics and surfactant constitution both influence the extent of biophysical inhibition of pulmonary surfactants.
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany. Electronic address: moritz.beck-broichsitter@innere.med.uni-giessen.de.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmehl
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
mesh_terms: D000327:Adsorption; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry*; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D010743:Phospholipids; D011137:Polystyrenes; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; C078272:SF-RI 1, bovine surfactant preparation; C521929:Venticute
keywords: 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol); BAL; BALF; Biophysical inhibition; DLS; DPPC; IC(50); LDA; LSA; MWCO; NP; PA; PBS; PDI; PL; PLM; PLM-B; POPG; PS; PS100+; PS100-; Polymeric nanoparticles; Pulmonary drug delivery; Pulmonary surfactant; S.D.; SDS-PAGE; SP; Surface activity; TEM; bronchoalveolar lavage; bronchoalveolar lavage fluid; c(NP); concentration of polymeric nanoparticles; dynamic light scattering; half maximal inhibitory nanoparticle concentration; large surfactant aggregates; laser Doppler anemometry; minimum surface tension during film oscillation; molecular weight cut-off; nanoparticles; negatively-charged poly(styrene) nanoparticles (nominal diameter: 100nm); p; palmitic acid; phospholipid mixture; phospholipid mixture supplemented with surfactant protein B; phospholipids; poly(styrene); polydispersity index; positively-charged poly(styrene) nanoparticles (nominal diameter: 100nm); probability value; pulsating bubble surfactometer; rSP; recombinant surfactant associated protein; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; standard deviation; surface tension after film adsorption; surfactant associated protein; transmission electron microscopy; γ(ads); γ(min)