(298c) Fabrication of Biodegradable Rod-Shaped Drug Carriers with Modified Two-Step Emulsion Solvent Evaporation Technique

There has been growing interest in recent years towards utilization of non-spherical particles for drug delivery applications. Rod-shaped particles have demonstrated reduced uptake by immune cells, increased circulation time and enhanced margination and binding to the vascular wall making them favorable compared to their spherical counterparts. Oil-in-water emulsion solvent evaporation, a simple and scalable technique for fabricating particulate carriers, has recently been applied to fabricate poly(lactic-co-glycolic) acid (PLGA) spheroids. However, this technique has been unable to generate small-sized rods applicable for usage in drug-delivery.

In this study, we have developed a two-step fabrication protocol enabling stretching of smaller sized droplets by separating the droplet formation and stretching steps and inducing a sudden increase in the viscosity and capillary number of the system. Evaluating different surface-active molecule and oil phase solvents demonstrated that sodium metaphosphate and chloroform are respectively the optimum choices for maximizing the fabrication yield of PLGA rods. With our optimized two-step fabrication protocol, we were able to generate PLGA rods with major and minor axis sizes as small as 3.2 µm and 700 nm. Nile Red loaded rods conjugated with targeting antibodies fabricated with our modified protocol were able to successfully bind to inflamed endothelium under shear flow. The in vitro and in vivo binding capability of the rods were evaluated and compared to spheres to demonstrate the effect of shape on the performance of biodegradable drug carriers.