Bioinspired particle engineering for non-invasive inhaled drug delivery to the lungs

Pulmonary drug delivery is governed by several biophysical parameters of delivery carriers, such as particle size, shape, density, charge, and surface modifications. Although much attention has been given to other parameters, particle shape effects have rarely been explored. In this work, we assess the influence of particle shape of inhaled delivery carriers on their aerodynamic properties and macrophage uptake by using polymeric microparticles of different geometries ranging in various sizes. Doxorubicin was conjugated to the polymer particles and the bioconjugates were characterized. Interestingly, the results of in-vitro lung deposition, performed using a next generation impactor, demonstrated a significant improvement in the aerodynamic properties of the rod-shaped particles with a high aspect ratio as compared to spherical particles with the same equivalent volume. The results of a macrophage uptake experiment demonstrate that the high aspect ratio particles were phagocytosed less than spherical particles. Furthermore, the cytotoxicity of these doxorubicin-conjugated particles was determined against murine macrophages, resulting in reduced toxicity when treated with high aspect ratio particles as compared to spherical particles. This project provides valuable insights into the influence of particle shape on aerodynamic properties and primary defense mechanisms in the peripheral lungs, while using polymeric microparticles of various sizes and geometries. Further systematic development can help translate these findings to preclinical and clinical studies for designing efficient inhalable delivery carriers.