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

A surface active layer consisting mainly of phospholipids lines the human c onducting airways. Dysfunction of this layer could play a role in the patho genesis of chronic obstructive airway diseases like asthma and chronic bron chitis. Replacement therapy with exogenous surfactants is being considered in such conditions. The relationship between surfactants and mucus viscosit y 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 stu dies the interaction of three therapeutic surfactants - Exosurf, ALEC and S urvanta; the main phospholipids of lung surfactant (1,2-dipalmitoyl phospha tidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol ( PG)) as well as their binary mixtures (PCPE and PCPG) in a PC:(PE or PG) ra tio of 2:3; on the viscosity of mucus gel simulants (MGS - a polymeric gel consisting mainly of gum tragacanth and simulating respiratory mucus). The surfactants were studied with respect to their ability to alter MGS viscosi ty at shear rates ranging from 0.1498 to 51.2 s(-1) in a concentric cylinde r viscometer at 37 degreesC. The change in viscosity of the MGS on incubati on with surfactant versus shear rate was found be non-Newtonian and to foll ow a power law model (coefficient of regression R-2 greater than or equal t o 0.9). The sheer rates experienced by a surfactant mixture, while passing through the tracheobronchial tree, were then calculated by modelling the tr acheobronchial tree as cylindrical branching tubes. The equation governing the flow of a power law fluid through a cylindrical pipe was used to determ ine the shear experienced by a surfactant infusion as it passes through var ious mucus lined branches of the tracheobronchial tree. The surfactants wer e then compared based on their ability to alter MGS viscosity at shear rate s corresponding to that of large, medium and small bronchi, as calculated b y the study. (C) 2001 Elsevier Science B.V. Ah rights reserved.