The Mechanism of Chitosan Enhanced Lung Surfactant Adsorption at the Air-Liquid Interface in the Presence of Serum Prote
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1061-MM10-03
The Mechanism of Chitosan Enhanced Lung Surfactant Adsorption at the Air-Liquid Interface in the Presence of Serum Proteins Patrick C Stenger, Omer M Palazoglu, and Joseph A Zasadzinski Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106-5080 ABSTRACT Pressure-area isotherms and fluorescence microscopy were used to investigate the impact of chitosan on the competitive adsorption between lung surfactant (LS) and serum proteins at the air-liquid interface. Isotherms demonstrate an optimum chitosan concentration to mediate LS adsorption; higher concentrations actually reduce the amount of LS which can adsorb. Fluorescence microscopy images show the transition from a serum protein to LS-covered interface for the optimum chitosan concentration; this transition goes through a sharply phase separated coexistence region. The results suggest that the cationic chitosan molecules mediate adsorption of the negatively charged LS aggregates by reducing the electrostatic barrier imposed by negatively charged interfacial serum proteins. INTRODUCTION Lung surfactant (LS) is a unique mixture of lipids and proteins that lines the alveolar air-liquid interface and lowers the surface tension in the lungs, thereby insuring negligible work of breathing and uniform lung inflation [1]. The absence of LS due to prematurity leads to Neonatal Respiratory Distress Syndrome (NRDS) which has been successfully treated in developed countries with animal-derived replacement LS [2]. In a related condition, the surface tension control imposed by LS is compromised during Acute Respiratory Distress Syndrome (ARDS) which afflicts 140,000 annually with a 40% mortality rate in the United States [3]. The complex pathogenesis of ARDS includes increased permeability of the alveolar-capillary barrier yielding an influx of blood serum proteins into the bronchial and alveolar fluid [4]. The animalderived replacement LS used to treat NRDS also loses its ability to reduce surface tension and is said to be “inactivated” when used to treat ARDS [5]. In vitro LS mixed with serum proteins shows an ARDS-like decrease in performance; surfactant inactivation caused by serum protein leakage into the alveoli is one reason why treatment of ARDS with replacement LS is unsuccessful [6]. One possible cause of LS inactivation is the competitive adsorption of surface-active serum proteins (such as albumin) that reduces or even eliminates the normal adsorption of LS to the interface [6]. Albumin is surface-active and has a saturation surface pressure, Π, (Π = γw-γ; γw is the surface tension of a clean air-water interface, 72 mN/m, and γ the measured surface tension) that is ~18 mN/m, much lower than the Π ∼70 (γ near zero) required for proper respiration [6]. This competitive adsorption of albumin to the alveolar air-liquid interface leads to a steric and electrostatic energy barrier to LS adsorption which can lower the rate of LS transport to the interface [7]. Several hydrophilic polymers, such as polyethylene glycol (PEG),
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