(578a) Engineering Shape of Drug Delivery Particles

Encapsulation of therapeutic drugs in polymeric particles offers several advantages over conventional formulations. Several properties of particles, including size, shape and surface chemistry, influence their performance in drug delivery applications. Although the effects of size and surface properties on particle performance have been studied in depth, little is known about the impact of particle shape on drug delivery. This limitation motivates our research. We specifically focus on the impact of particle shape on phagocytosis – clearance of particles by macrophages which offers a formidable challenge to particle-mediated drug delivery.

We fabricated various shapes of polymeric microparticles including prolate ellipsoids, oblate ellipsoids, elliptical disks, rectangular disks, UFOs, rods, and many other peculiar shapes. Collectively, these particles possess volumes, surface areas, curvatures and maximum lengths that span several orders of magnitude. Most of these shapes have not been made before. Using an alveolar macrophage cell line as model macrophages, we study how macrophages interact with particles possessing various shapes. We utilize video microscopy and scanning electron microscopy to observe how the macrophage membrane moves on the particle surface. We also use immunostaining to visualize how actin polymerization, which drives membrane motion beneath the membrane, is affected by shape and thus dictates the success of phagocytosis. The results show that particle shape, from the point of view of macrophage, profoundly impacts phagocytosis. While macrophages actively ingest particles with certain shapes from their perspective, they simply spread on others.

This is an interesting example of cell behavior being dictated by the substrate shape. The results of this work will not only help in better understanding the biophysics of phagocytosis, but will offer insight into designing particles to either avoid or enhance phagocytosis. In a broader sense, this work will add a new dimension to particle design and will facilitate fabrication of the next generation of drug delivery carriers.