Effect of hyaluronic acid on the performance of pulmonary surfactant. Towards the production of enhanced clinical surfactant formulations

Abstract

In order to prevent alveolar collapse, the surface tension at the air-liquid interface of alveoli has to be minimized at the end of expiration. Pulmonary surfactant, a lipid-protein complex synthetized and secreted by type II pneumocytes, adsorbs into the alveolar surface to form highly surface-active interfacial films. Lack or inactivation of surfactant is associated with severe respiratory pathologies, some of them treated by supplementation with exogenous surfactant formulations. It has been demonstrated that surfactant is assembled by pneumocytes in a highly packed dehydrated state that unravels once secreted to exhibit optimal interfacial capacities. Once exposed to air and subjected to dynamic breathing, surfactant can be isolated from bronchoalveolar lavages (BAL) in more unpacked and relatively hydrated stages. In this work we have used different biophysical techniques, such as surface balances and fluorescence spectroscopy to show how BAL surfactant pre-exposed to certain polymers such as hyaluronic acid (HA) transits to a more stably packed state with improved functional capabilities that approach those of freshly secreted surfactant that had never been exposed to air, such as the surfactant that can be purified from amniotic fluid. These results open new opportunities to develop more efficient therapeutical surfactant preparations to treat respiratory pathologies still unresolved.