Towards Regionarl and Targeted Deposition in the Pulmonary Acinus

In recent years, the use of magnetic particles for regional and targeted delivery to the lungs has gained increased interest. In particular, by coupling magnetic particles to inhaled drug particles aerosol deposition can be increased regionally or locally to a specific point. Although this method has been proven viable in seminal animal studies, it is still unclear what constitutes optimal formulations for drug delivery. Moreover, the transport of such particles in the acinar regions of the lungs is still poorly characterized from a mechanistic and fluid dynamic standpoint.

Here, we revisit the problem of magnetic particle delivery to the deep acinar regions of the lungs in an effort to uncover detailed transport characteristics and optimal drug formulations. We have simulated airflow and particle transport in an anatomically inspired, asymmetric, 6-generation acinar tree, under various inhalation conditions and magnet operating scenarios. To study the effect of the magnetic force, liquid droplets (0.5–3 μm diameter) were loaded with different amounts of magnetic material volume fractions (i.e. using SPIONs). Our numerical results highlight that deposition efficiency can be dramatically increased using magnetic particles; while a deep breath helps bring the particles deeper, a breath-hold maneuver can help reduce the amount of needed magnetic material. Turning the magnet on only during the breath-hold significantly improves aerosol dispersion. We use our results to support the idea that conditions which yield the worst deposition results in the non-magnetic case (i.e. 0.5 μm droplets and a quiet breathing maneuver) might represent an attractive strategy for magnetic targeting. Finally, we discuss therapeutic applications of our results for regional and targeted delivery in the acinus.