Interfacial behavior of pulmonary surfactant preparations containing egg yolk lecithin.

Mammalian lungs are covered with lipid-protein complexes or pulmonary surfactants. In this work, which aimed towards the less expensive production of artificial pulmonary surfactants, we produced surfactants composed of egg yolk lecithin (eggPC), palmitic acid, and hexadecanol (= 0.30/0.35/0.35, mol/mol/mol ) containing different amounts of Hel 13-5 (NH2-KLLKLLLKLWLKLLKLLL-COOH) as a substitute for the proteins in native pulmonary surfactants. Surface pressure (π)-molecular area (A) and surface potential (DV)-A isotherms of the mixtures were measured via the Wilhelmy and ionizing (241)Am electrode methods, respectively. The interactions between the lipid components and Hel 13-5 led to variations in the surface pressure caused by the expulsion of fluid components from the surface. Furthermore, the π-A and DV-A isotherms featured large hysteresis loops for the surfactant that contained a small amount of Hel 13-5 during compression and successive expansion cycling. To elucidate the morphology, the phase behavior was visualized in situ at the air-water interface by means of fluorescence microscopy; the images suggested less effective interactions between Hel 13-5 and the unsaturated PC in eggPC despite the similarity of their monolayer properties.

Miscibility of egg yolk lecithin with palmitic Acid and hexadecanol at the air-water interface.

The miscibility of Langmuir monolayers of egg yolk lecithin (eggPC) with n-hexadecanoic acid (PA), 1-hexadecanol (HD), and their equimolar mixture (PA/HD) was investigated thermodynamically and morphologically. Surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms for the binary and ternary systems were measured, employing the Wilhelmy method and the ionizing (241)Am electrode method, respectively. From the thermodynamic perspective, eggPC was partially miscible with PA, HD, and PA/HD within the monolayer state, in terms of an excess Gibbs free energy of mixing calculated from the π-A isotherms and a two-dimensional phase diagram based on a monolayer collapse pressure. This was also directly supported by phase behavior observations using fluorescence microscopy (FM). EggPC formed a typical liquid-expanded (LE) monolayer, and the others formed liquid-condensed (LC) monolayers. The FM images exhibited miscible modes at middle molar fractions of PA, HD, and PA/HD, and immiscible patterns at large molar fractions for all the systems examined. A new finding in the present study was that the eggPC/PA, eggPC/HD, and eggPC/(PA/HD) systems exhibited partial miscibility, although the systems were made of both LE (eggPC) and LC monolayers (the others). This miscibility is considered to be attributable to the molecular species comprising eggPC.

[Study of novel artificial lung surfactants incorporating partially fluorinated amphiphiles].

Lung surfactants (LS), a complex of ∼90 wt% lipids (mainly dipalmitoylphosphatidylcholine or DPPC) and ∼10 wt% surfactant proteins (SP-A, -B, -C, and -D), adsorb to an air-alveolar fluid interface and then lower its surface tension down to near zero during expiration. Intratracheal instillation of exogenous LS preparations can effectively compensate for surfactant deficiency in premature infants with respiratory distress syndrome (RDS). Surfacten® (Mitsubishi Tanabe Pharma Corporation, Osaka, Japan), a modified bovine lung extract and an effective surfactant replacement in treatment for RDS patients, is supplemented with DPPC, palmitic acid, and tripalmitin. For the premature infants suffering from RDS, instillation of Surfacten® leads to a dramatic improvement in lung function and compliance. Herein, the author reviews potential use of newly designed preparations containing a mimicking peptide of SP-B and also introduces the current research on the preparations incorporated with partially fluorinated amphiphiles to improve their efficacy.

Development of low cost pulmonary surfactants composed of a mixture of lipids or lipids-peptides using higher aliphatic alcohol or soy lecithin.

The artificial pulmonary surfactant composition in the present study is characterized by a lipid mixture system composed of higher aliphatic alcohol, egg yolk phosphatidylcholine (egg PC), soy lecithin and higher aliphatic acid as the major components or a peptide-lipid mixture system composed of a combination of the lipid mixture system to which a peptide is added. Three peptides with amphiphilic surface-staying, membrane spanning, and both properties were designed and synthesized. The evaluation of pulmonary surfactant assay was performed by a hysteresis curve drawn upon the measurement for the surface tension-area curve with the Wilhelmy surface tensometer in vitro and the recovery of lung compliance for the pulmonary surfactant-deficient rat models in vivo. Lipid-mixture systems composed of octadecanol or soy lecithins containing no peptide were favorable hysteresis curves as compared with commercially available Surfacten, but were not prominent. The peptide-lipid mixture systems composed of a combination of the lipid mixture of alkyl alcohol or soy lecithin to which peptides designed were added were desirable hysteresis curves similar to Surfacten and amphiphilic Hel 13-5 peptide-lipids mixture systems were much more effective than the lipid mixture system. Particularly, the recovery of lung compliance treated with hydrogenated soy lecithin-fractionated soy lecithin PC70-palmitic acid-peptide Hel 13-5 (40:40:17.5:2.5, w/w) was comparable to that with Surfacten. Because the artificial pulmonary surfactant compositions of this study can be prepared at lower costs, they are useful for the treatment of respiratory distress syndrome and acute respiratory distress syndrome as well as for inflammatory pulmonary diseases, dyspnea caused by asthma, etc.