(105a) Fabrication of Biocompatible Particles with Tunable Shapes and Surfaces By the Addition of Resveratrol to Oil in Water Emulsions

Particles for biomedical applications can be produced by emulsifying biocompatible polymers dissolved in an organic solvent in water. The emulsion is then transferred to an extraction bath that removes the solvent from the dispersed droplets, which leads to polymer precipitation and particle formation. Typically, the particles are smooth and spherical, likely because the droplets remain fluid throughout the solvent extraction process allowing minimization of surface area as the volume decreases. Few modifications to this technique exist that alter the spherical geometry, even though particle performance, from drug delivery to engaging cells of the immune system, can be controlled with morphology. Here we demonstrate that incorporation of resveratrol and a cosolvent into an emulsion of poly(lactide-co-glycolide) and dichloromethane in aqueous poly(vinyl alcohol) leads to a “crumpled” particle morphology. Video microscopy of particle formation indicates that during solvent extraction the droplet crumples in on itself, suggesting that resveratrol endows the droplet surface with solid-like properties. Particle morphology can be tuned from that of a crumpled sheet of paper to deflated beach balls based on cosolvent. In addition, degree of crumpling can be controlled by resveratrol concentration or by switching out resveratrol for other stilbenes with various hydroxyl substitutions. Finally, this approach to form nonspherical particles extends to other polyesters including polycaprolactone and polylactic acid. Taken together, we demonstrate a novel fabrication technique to control the morphology of biocompatible polymer particles. The methodology reported will enable applications in which a deviation from the default smooth, spherical geometry is desired.