Lipid-based mucus penetrating nanoparticles and their biophysical interactions with pulmonary mucus layer

Lungs are critical organs that are continuously exposed to exogeneous matter. The presence of the mucus layer helps to protect them via its adhesive structure and filtering mechanisms. Mucus also acts as a strong barrier against the drugs and nanocarriers in drug delivery. In this study, solid lipid nanoparticles (SLNs), at different sizes and surface properties, were prepared and their spreading/penetration ability was tested for their use in pulmonary drug delivery. The biophysical interactions of SLNs have been studied via light scattering (LS) and zeta potential analyses by incubating the SLNs in mucin solution and forming a model mucus layer using a Langmuir-Blodgett (LB) trough. In addition, the penetration performance of the particles was evaluated using Franz diffusion cell and rotating diffusion tubes. It was determined that 36% of SLNs can penetrate through a 1.2 +/- 0.2-mm-thick mucus layer. Finally, the spreading behavior of the particles on a mucus-mimicking subphase was characterized and enhanced using a catanionic surfactant mixture. Overall, the current study was the first to investigates both the spreading and penetration performance of SLNs. The developed systems offer a drug delivery system that is able to achieve high penetration rates through a thick mucus layer.