Structure and Thermotropic Behavior of Bovine- and Porcine-Derived Exogenous Lung Surfactants

Abstract

Two commercial exogenous pulmonary surfactants, Curosurf and Survanta, are investigated. Their thermotropic behavior and associated structural changes for the samples in bulk are characterized and described. For Survanta, the obtained results of differential scanning calorimetry showed a thermogram with three peaks on heating and only a single peak on cooling. Curosurf on the other hand, presents calorimetric thermograms with only one peak in both the heating and cooling scans. This distinct thermotropic behavior between the two pulmonary surfactants, a consequence of their particular compositions, is associated with structural changes that were evaluated by simultaneous small- and wide-angle X-ray scattering experiments with in situ temperature variation. Interestingly, for temperatures below ∼35 °C for Curosurf and ∼53 °C for Survanta, the scattering data indicated the coexistence of two lamellar phases with different carbon chain organizations. For temperatures above these limits, the coexistence of phases disappears, giving rise to a fluid phase in both pulmonary surfactants, with multilamelar vesicles for Curosurf and unilamellar vesicles for Survanta. This process is quasi-reversible under cooling, and advanced data analysis for the scattering data indicated differences in the structural and elastic properties of the pulmonary surfactants. The detailed and systematic investigation shown in this work expands on the knowledge of the structure and thermodynamic behavior of Curosurf and Survanta, being relevant from both physiological and biophysical perspectives and also providing a basis for further studies on other types of pulmonary surfactants.

A recipe for a good clinical pulmonary surfactant

“…if they are rich in fully saturated fatty acids with no double bonds, the monolayer can even reach extremely low surface tensions, close to 0 mN/m, at least when they are compressed in vitro. However, surfactant films at the airways typically present a complex three-dimensional multilayered structure, connected with a rich network of membranes into the subphase [ [13] , [14] , [15] ] [see cartoon in Fig. 1 ].…”

“…Once established that a lipid/protein extract obtained from a natural surfactant could be reconstituted to a suspension with the ability to efficiently form surface-active films, and thus serve in facilitating opening and stabilization of preterm lungs, the golden age of surfactant therapy was opened [ [1] , [2] , [3] , [4] ]. The different natural clinical surfactants still in use were variations in the way to prepare a extract of the most hydrophobic components of surfactant using organic solvents applied to different materials of animal origen [ 49 ], and were able to reproduce much of the complex multilayered structure of surfactant suspensions and films [ 13 ]. As summarized in Table 1 , all the materials that ultimately worked had in common the presence of enough amounts of the hydrophobic surfactant proteins, although varied in their relative amount, as well as in the qualitative and quantitative lipid composition, which depended strongly on the starting material (BAL or whole minced lungs) and on the way the organic extract was processed and purified to become a standardized product.…”

Pulmonary antimicrobial photodynamic therapy and the role of the lung surfactant

“…77 The lung surfactant (LS) is a mixture of phospholipids and proteins that prevent the alveoli from collapsing and enables the gas exchange by decreasing the surface tension of the air-water interface in the hypophase. [78][79] It also acts as a barrier, protecting the organism from contaminants in the air. [79][80] It is synthetized, processed, packaged, secreted and recycled by type II pneumocytes.…”

“…[78][79] It also acts as a barrier, protecting the organism from contaminants in the air. [79][80] It is synthetized, processed, packaged, secreted and recycled by type II pneumocytes. 77 Figure 6 depicts the alveolar microenvironment, in which the lung surfactant is present.…”

“…The lung surfactant is a mixture of phospholipids and proteins that is expressed by the lung epithelium and presents two main purposes: enabling the gas exchange by decreasing the surface tension of the airwater interface; and protecting the organism from contaminants in the air. 78,79 The decreased efficacy of antibiotics and other drugs in the presence of lung surfactant has been thoroughly reported in the literature. [82][83][84]86,[119][120][121] To investigate this possibility, five photosensitizers with potential for aPDT applications in the lungs had their efficacy in killing the pneumoniacausing Streptococcus pneumoniae tested in the presence and absence of a medical grade lung surfactant.…”