Biophysical and gas transfer properties of lung surfactant and polymer-enhanced lung surfactant films

Description

Lung surfactant is a complex mixture of approximately 90% lipids and 10% proteins. It lines a thin film on the air-water interface of alveoli and plays a crucial role in maintaining the normal respiratory mechanics by reducing the alveolar surface tension to near-zero values. Deficiency or dysfunction of lung surfactant causes respiratory distress syndrome (RDS), one of the major contributors to neonatal morbidity and mortality in industrialized countries. Exogenous surfactant replacement therapy has been used as a standard therapeutic intervention for patients with RDS. Different formulations, either synthetic or natural surfactants extracted from mammalian lungs, have been developed as surfactant substitutions. A focal point in these developments is the use of certain water-soluble polymers (e.g., polyethylene glycol (PEG)) as additives to therapeutic surfactants to enhance their surface activity and resistance to various inhibitory substances, such as blood proteins and meconium.The clinical applications of lung surfactant entail the in vitro assessment of its biophysical properties, i.e., properties related to highly dynamic and very low surface tensions. Accuracy, versatility, and simplicity of Axisymmetric Drop Shape Analysis (ADSA) facilitate lung surfactant related studies. This dissertation systematically studies the biophysical and gas transfer properties of lung surfactant and polymer-enhanced lung surfactant films using ADSA. Main contributions fall into the following four headings: (1) Development of ADSA-Captive bubble (ADSA-CB) for studying lung surfactant-polymer systems. (2) Development of a methodology capable of simultaneously measuring surface tension and interfacial gas transfer, which allows the study of gas permeability of compressed lung surfactant films, even at very low surface tensions. This study provides direct evidence that the surfactant lining layer of alveoli may play a role in pulmonary gas exchange. (3) Study of the effect of environmental humidity on surface activity of lung surfactant films. This study necessitates careful humidity control in all in vitro assessment of lung surfactant. (4) A cationic natural polymer, chitosan, is tested as a novel lung surfactant additive. This study suggests that chitosan may be a more effective polymeric additive than the nonionic polymers tested so far. These findings have strong implications for the development of new formulations for surfactant replacement therapy.

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