(38c) Shape-Shifting Particles for Drug Delivery

Size and surface chemistry have traditionally served as two dominating design parameters of drug delivery carriers. In the last few years, however, there has been growing recognition that shape is a key parameter that dictates applications of polymeric carriers for drug delivery. Nevertheless, the field of shape engineering is still in its infancy and comprehensive role of particle shape in drug delivery is yet to be understood.

Herein we investigated the role of shape in achieving two important functions in drug delivery: avoiding phagocytosis in macrophages and promoting endocytosis in target cells. Particles were synthesized from PLGA with two shapes, spheres and elliptical disks, and their internalization was studied in murine macrophages and endothelial cells (human umbilical vein endothelial cells). The results showed that macrophages as well as endothelial cells favored elliptical disks over spheres for internalization by a factor of about four. While reduced phagocytosis of elliptical disks by macrophages is highly desired, reduction of endocytosis due to the same morphological features is undesired.

To address this challenge, shape-shifting particles were developed. These particles were initially elliptical disk-shaped and changed their shape to spheres over time. The degree and the rate of the shape change depend on several factors including glass transition temperature, intrinsic viscosity, particle size and environmental temperature. By controlling these parameters, particles were made to change their shape over a time ranging from a few minutes to a few days. The ability to change the shape of particles in real time upon administration into the body provides an additional parameter to engineer polymeric carriers for applications in drug delivery.