(629a) Design and Characterization of Synthetic Lung Surfactants for Adsorption to Clean and Serum Protein Covered Interfaces | AIChE

(629a) Design and Characterization of Synthetic Lung Surfactants for Adsorption to Clean and Serum Protein Covered Interfaces

Authors 

Stenger, P. C. - Presenter, University of California Santa Barbara
Vestal, J. M. - Presenter, NC State University
Zasadzinski, J. A. - Presenter, University of California
Waring, A. J. - Presenter, University of California, Los Angeles


Lung surfactant (LS) is a unique mixture of lipids and proteins (SP-A, SP-B, SP-C, SP-D) that lines the alveoli and lowers the surface tension in the lungs, thereby insuring a negligible work of breathing. The adsorption of LS to the alveolar air-liquid interface is strongly inhibited by the competitive adsorption of surface active serum proteins such as albumin, and is likely the explanation of surfactant inactivation in Acute Respiratory Distress Syndrome (ARDS). In vitro, the adsorption of animal derived replacement LS to the interface is restored by hydrophilic polymers such polyethylene glycol (PEG), suggesting a promising therapy for ARDS. Here synthetic LS formulations designed to mimic the animal derived LS are designed and evaluated in terms of albumin inhibition and response to hydrophilic polymers. Synthetic LS mixtures yield surface pressure-area isotherms which are similar to animal derived LS formulations on a clean (albumin free) subphase and show similar albumin inhibition. However, only when the albumin concentration is reduced ten fold do some of the synthetic LS formulations, those which contain a mimic of SP-C, significantly enhance LS adsorption. Fluorescence microscopy images show that both the SP-B and SP-C mimics facilitate the synthetic LS breaking through the albumin film to coexist as immiscible albumin and LS domains. However, the albumin is only expelled from the interface for formulations containing the SP-C mimic. The current study shows that enhanced transport to the interface by the PEG is insufficient to reverse albumin inhibition if the LS does not contain the proper proteins. More generally, these results also demonstrate a method to more robustly evaluate future SP-B and SP-C protein mimics.