Synthetic surfactant based on analogues of SP-B and SP-C vs single-peptide surfactants and natural surfactant: an experimental study

Surfactant replacement therapy is the mainstay treatment for neonatal respiratory distress syndrome. Natural surfactant has a very complex composition consisting of four specific proteins (SP-A, SP-B, SP-C, and SP-D) and several species of phospholipids. Attempts to develop a synthetic pulmonary surfactant have met several difficulties, in particular in the synthesis of SP-B and SP-C proteins, which are responsible for the surface properties of the surfactant. All synthetic surfactants analyzed so far contain comparatively simple lipid mixtures with a single peptide designed to mimic SP-B or SP-C. Although some of these preparations have shown activity similar to natural derived surfactant preparations in increasing lung compliance, they proved to be inferior in terms of alveolar stability at end-expiration. Of note, the efficacy of an exogenous surfactant is dependent upon both its ability to increase lung compliance and to prevent alveolar collapse. Moreover, results of recent studies have indicated that SP-B and SP-C play different roles in pulmonary physiology, suggesting that both proteins are required for alveolar stabilization at the end of expiration.
On this basis, an animal study was conducted to evaluate the efficacy of fully synthetic surfactants containing SP-B and SP-C analogues compared to single-peptide surfactants. In particular, premature newborn rabbits treated with synthetic surfactants were ventilated for 30 min without positive end-expiratory pressure, which can contribute to preventing alveolar collapse thus confounding proper evaluation of surfactants. Animals receiving Curosurf served as positive controls and non-treated littermates as negative controls.
Treatment with a synthetic surfactant containing SP-B and SP-C analogues gave significantly better lung gas volumes than single-peptide surfactant, however the results were still inferior as compared to Curosurf (Curosurf: 15–17 ml/kg; 2% Mini-B [a short-cut version of SP-B] and 2% SP-C33: 8–9 ml/kg, 2% Mini-B or 2% SPC33: 3–4 ml/kg). In addition, animals treated with Curosurf showed a significantly higher grade of alveolar expansion than all other groups and statistically significant less epithelial necrosis than non-treated controls.
In conclusion, the present results are encouraging for the development of a fully synthetic surfactant that can be used in replacement therapy and prove that both SP-B and SP-C analogues are required for obtaining a superior stabilization of alveoli at the end of expiration. However, functional and histological data still point to Curosurf, a natural derived surfactant, as the treatment providing superior results as compared to any of the synthetic mixtures analyzed. According to these findings and other recent studies, it is suggested that lipid composition is another variable that needs further improvement for the optimization of synthetic surfactants.

Top