Basic research and development of de novo-designed peptide/fluorinated carbon hybrid artificial lung surfactant

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This study is aimed to investigate the interfacial behavior of a mimic peptide (Hel/3-5) of human surfactant protein B, in a phospholipid (DPPC) and various lipid mixtures and to examine the correlation between in vitro surface activity and in vivo lung function of artificial surfactant preparation. The new finding is following terms.I: DPPC alone has some defects in pulmonary functions such as rapid respreading, adsorption, and large hysteresis. However, addition of a small amount of He113-5 to DPPC led to improvement in adsorption of DPPC, and enlargement of a hysteresis of surface pressure (π)-area (A) curve for DPPC reversibly, as shown a substitute for SP-B.II: Additive PG works selectively and electrostatically interact with cationic Hel13-5 during the squeeze-out process and then 3-D aggregates containing Hel13-5 and being formed just below the surface monolayer. This formation contributes to the stability of DPPC monolayers. On the other hand, PA components are not mainly squee … More zed out of surface monolayers together with He113-5, and form the close-packed monolayer with DPPC at the interface.III: Surface chemistry (Langmuir isotherms, fluorescent images, temperature dependence, and hysteresis curves) of the artificial preparation and Surfacten (commercially available for RDS patients) has been made for the comparison between them. Above all, this artificial preparation is comparative to Surfacten in terms of surface activity and the interfacial behavior.IV: In vivo, efficacy of this preparation was elucidated in a rat lung and a surfactant-deficient rat. The preparations containing 2.5wt% Hel13-5 was used for the in vivo measurements of dynamic lung compliances and quasi-static pressure-volume curves. The preparation with 2.5wt% Hel13-5 was equivalent to Surfacten with respect to improving lung function and mechanics for the surfactant-deficient rat.Finally, this pulmonary surfactant substitutes will contribute to tailoring surfactant preparations to various states of surfactant deficiency, insufficiency and inactivation. Less