Effect of phospholipid mixtures and surfactant formulations on rheology of polymeric gels, simulating mucus,at shear rates experimenced in the tracheobronchial tree

摘要

A surface active layer consisting mainly of phospholipids lines the human conducting airways. Dysfunction of this layer could playa role in the pathogenesis of chronic obstructive airway diseases like asthma and chronic bronchitis. Replacement therapy with exogenous surfactants is being considered in such conditions. The relationship between surfactants and mucus viscosity would be important for such an application. Respiratory mucus is composed of high molecular weight glycoprotein molecules which form temporary cross-links and entanglements to form a gel-like material. The present paper studies the interaction of three therapeutic surfactants -Exosurf, ALEC and Survanta; the main phospholipids of lung surfactant (1,2-dipalrnitoyl phosphatidylcholine (PC), phosphatidylethanolarnine (PE) and phosphatidylglycerol (PO)) as well as their binary mixtures (PCPE and PCPO) in a PC:(PE or PO) ratio of 2:3; on the viscosity of mucus gel simulants (MOS -a polymeric gel consisting mainly of gum tragacanth and simulating respiratory mucus). The surfactants were studied with respect to their ability to alter MOS viscosity at shear rates ranging from 0.1498 to 51.2 S-I in a concentric cylinder viscometer at 37°C. The change in viscosity of the MOS on incubation with surfactant versus shear rate was found be non-Newtonian and to follow a power law model (coefficient of regression R2 ~ 0.9). The shear rates experienced by a surfactant mixture, while passing through the tracheobronchial tree, were then calculated by modelling the tracheobronchial tree as cylindrical branching tubes. The equation governing the flow of a power law fluid through a cylindrical pipe was used to determine the shear experienced by a surfactant infusion as it passes through various mucus lined branches of the tracheobronchial tree. The surfactants were then compared based on their ability to alter MOS viscosity at shear rates corresponding to that of large, medium and small bronchi, as calculated by the study.