Utilizing the Lung as aModel to Study Nanoparticle-Based Drug Delivery Systems.

Abstract

Intranasal administration is a highly effective route for drug delivery and biodistribution studies. Indeed, this route of delivery has become the method of choice to distribute diverse pharmacological agents both locally and systemically. In the majority of preclinical animal models and in human patients, intranasal administration is the preferred method to deliver therapeutic agents to the airways and lungs. However, issues with drug stability and controlled release in the respiratory tract are common problems with many therapeutic agents. Nanoparticle delivery via intranasal administration has tremendous potential to circumvent these common issues. Over the past 30years nanoparticles have gained increased interest as therapeutic delivery vehicles and as tools for improved bioimaging. Integral to the success of nanoparticles in drug delivery and biodistribution is the utilization of mouse models to characterize therapeutic strategies under physiologically relevant in situ conditions. Here, we describe a model of nanoparticle administration to the lungs utilizing intranasal administration and discuss a variety of highly useful techniques to evaluate nanoparticle up-take, biodistribution, and immune response. While these protocols have been optimized for intranasal administration of common fluorescently labeled nanoparticles, they can be applied to any nanoparticle or drug delivery system of interest targeting the lungs and airways.