(118d) The Mechanism Of Chitosan Induced Enhancement Of Lung Surfactant Adsorption

Chitosan is a biocompatible cationic polysaccharide derived from deacetylated chitin whose membrane perturbing properties make it widely investigated as a non-viral DNA delivery vehicle. This paper will exploit chitosan's bilayer perturbing properties in a different system and demonstrate how the biopolymer enhances surfactant adsorption to the air-liquid interface. The adsorption of lung surfactant (LS) bilayer aggregates to an air-liquid interface is strongly inhibited by the competitive adsorption of surface active serum proteins and is likely the explanation of LS inactivation in Acute Respiratory Distress Syndrome (ARDS). Utilizing a cycling Langmuir trough as an in vitro model to approximate LS/serum protein behavior at alveolar interface, we show that LS adsorption to the interface is restored by chitosan addition suggesting a promising therapy for ARDS. Fluorescence microscopy images show distinct changes in interfacial morphology between serum protein and LS-covered regions offering a visual confirmation of surfactant adsorption to the interface. LS is ~70 wt % dipalmitoylphosphatidylcholine (DPPC) and freeze fracture transmission electron microscopy images of DPPC vesicles treated with chitosan show distinct morphological changes. Untreated DPPC vesicles are ~50 nm in diameter and uniformly distributed through the solution while a low concentration of chitosan (0.005 mg/mL) causes aggregation of the vesicles. At higher chitosan concentrations (0.5 mg/mL), images show numerous ~50 nm vesicles entrapped inside a larger vesicle, similar to ?vesosomes? used for drug delivery. These morphological changes induced by chitosan suggest that it enhances LS adsorption by facilitating the bilayer to monolayer transition at the interface.