Differential Interactions of Gelatin Nanoparticles with the Major Lipids of Model Lung Surfactant: Changes in the Lateral Membrane Organization

There has been an increasing interest in the potential of nanomedicine, particularly in the use of nanoparticles between 10 nm and 1 mu m in diameter as drug delivery vehicles. For pulmonary drug delivery, it is important to understand the effect of polymeric nanoparticles on the lung surfactant in order to optimize the carriers by reducing their potential toxicological effects. This work presents a biophysical study of the impact of gelatin nanoparticles on packing and lateral organization of simple and complex lipid layers containing the major components of lung surfactant. Zwitterionic phosphatidylcholines, negatively charged phosphatidylglycerols, and the sterol cholesterol were employed in the models. In addition, the impact of acyl chain length was investigated. Packing was determined by surface pressure-area isotherms, whereas direct imaging of the surfactant at the air-water interface was performed using Brewster angle microscopy. Our results indicate minor changes in the surface pressure-area isotherms but concomitantly significant effects on the lateral organization of the monolayers upon nanoparticle addition. The data also suggest differential interactions of nanoparticles with the major lipid classes. Gelatin nanoparticles interact stronger with negatively charged phosphatidyl-glycerols compared to zwitterionic phosphatidyl-cholines. Furthermore, charge distribution depending on the molar lipid ratio and acyl chain saturation is important as well. Even cholesterol, whose concentration is low compared to other components, plays an important role in nanoparticle interactions.