Biomimetic pulmonary surfactants

McLean, Larry R.; Lewis, Jon

doi:10.1016/0024-3205(94)00902-3

Cited by 12 publications

(8 citation statements)

References 115 publications

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“…Admixtures of DPPC and variable proportions of these simple peptides had enough surface activity to mimic pulmonary surfactant in animal models of surfactant deficiency [89][90][91][92]. This evidence provides support for the idea that a clinical surfactant could, in principle, be produced by a proper combination of lipids and synthetic peptides.…”

mentioning

confidence: 52%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

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Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration.Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material.In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed. Pulmonary surfactant function and dysfunctionThe respiratory surface of lungs constitutes the largest area of the human body exposed to the environment. Efficient gas exchange requires a large enough surface to be continuously exposed to air while minimising the barriers for oxygen and carbon dioxide to diffuse between air and the blood compartment [1]. At the same time, a selection of combined defence mechanisms is required to help keep such an essentially exposed area sterile of potential pathogenic microorganisms. Pulmonary surfactant, a lipid-protein complex produced by the alveolar epithelium of lungs, has been optimised to coordinate two main activities through natural evolution. On the one hand, it stabilises the respiratory surface against physical forces, therefore minimising the work required to maintain the large respiratory surface open to air [2][3][4]. On the other hand, pulmonary surfactant contains elements responsible for establishing a primary innate antipathogenic barrier, essential to ensure an intrinsically low pathogen load in the absence of induced defence mechanisms [5]. Extensive research in the last few decades has revealed some of the molecular mechanisms involved in pulmonary surfactant action. However, the manner in which both the biophysical and defence activities are intermingled and coordinately modulated in the alveolar spaces is now only beginning to be envisioned.Pulmonary surfactant is composed of approximately 90% lipids and 8-10% proteins, although only around 5% ...

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mentioning

confidence: 52%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

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“…KL4), which have also been successfully used in neonates [210]. These approaches were reviewed recently [211]. The enrichment of first generation surfactants with the hydrophilic SP-A successfully increased the resistance of the preparation to inactivation by oedema fluid [212].…”

Section: Future Aspects In Surfactant Therapymentioning

confidence: 99%

Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Dai¹,

Guzman²,

Costabel³

1999

Eur Respir J

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“…Such lipid-protein mixtures have potential for use as artificial surfactants in PS replacement therapies (Smith et al, 1988;Suzuki et al, 1986;Tanaka et al, 1986) for treating patients with surfactant disorders and deficiencies, such as occur in respiratory distress syndrome. Furthermore, synthetic peptides from various structural domains of SP-B and SP-C in conjunction with DPPC can reproduce some of the surface properties of native PS (see McLean and Lewis, 1995, for review). From in vitro dynamic cycling experiments of monolayers containing DPPC and SP-B or SP-C, it was suggested that such films can easily attain high 7T.…”

Section: Introductionmentioning

confidence: 99%

Combinations of fluorescently labeled pulmonary surfactant proteins SP-B and SP-C in phospholipid films

Nag¹,

Taneva²,

Pérez‐Gil³

et al. 1997

Biophysical Journal

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Hydrophobic pulmonary surfactant (PS) proteins B (SP-B) and C (SP-C) modulate the surface properties of PS lipids. Epifluorescence microscopy was performed on solvent-spread monolayers of fluorescently labeled porcine SP-B (R-SP-B, labeled with Texas Red) and SP-C (F-SP-C, labeled with fluorescein) in dipalmitoylphosphatidylcholine (DPPC) (at protein concentrations of 10 and 20 wt%, and 10 wt% of both) under conditions of cyclic compression and expansion. Matrix-assisted laser desorption/ionization (MALDI) spectroscopy of R-SP-B and F-SP-C indicated that the proteins were intact and labeled with the appropriate fluorescent probe. The monolayers were compressed and expanded for four cycles at an initial rate of 0.64 A2 x mol(-1) x s(-1) (333 mm2 x s x [-1]) up to a surface pressure pi approximately 65 mN/m, and pi-area per residue (pi-A) isotherms at 22 +/- 1 degrees C were obtained. The monolayers were microscopically observed for the fluorescence emission of the individual proteins present in the film lipid matrix, and their visual features were video recorded for image analysis. The pi-A isotherms of the DPPC/protein monolayers showed characteristic "squeeze out" effects at pi approximately 43 mN/m for R-SP-B and 55 mN/m for F-SP-C, as had previously been observed for monolayers of the native proteins in DPPC. Both proteins associated with the expanded (fluid) phase of DPPC monolayers remained in or associated with the monolayers at high pi (approximately 65 mN/m) and redispersed in the monolayer upon its reexpansion. At comparable pi and area/molecule of the lipid, the proteins reduced the amounts of condensed (gel-like) phase of DPPC monolayers, with F-SP-C having a greater effect on a weight basis than did R-SP-B. In any one of the lipid/protein monolayers the amounts of the DPPC in condensed phase were the same at equivalent pi during compression and expansion and from cycle to cycle. This indicated that only minor loss of components from these systems occurred between compression-expansion cycles. This study indicates that hydrophobic PS proteins associate with the fluid phase of DPPC in films, some proteins remain at high surface pressures in the films, and such lipid-protein films can still attain high pi during compression.

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Biomimetic pulmonary surfactants

Cited by 12 publications

References 115 publications

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Combinations of fluorescently labeled pulmonary surfactant proteins SP-B and SP-C in phospholipid films

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