(182z) Controlling Morphology of Biodegradable Polymer Particles with Bioactive Small Molecules and Its Application in Modulating Adipose Tissue Function

Authors: 
Isely, C., University of South Carolina
Gower, M., University of South Carolina
Many drugs are small molecules that suffer from poor bioavailability or severe off-target side effects; therefore, an important therapeutic strategy is encapsulating these drugs into biodegradable polymer particles for drug delivery directly to the tissue of interest. These particles are often fabricated using an oil-in-water emulsion/solvent extraction technique. This process involves suspending oil droplets consisting of an organic solvent, polymer and drug dispersed in a continuous phase of water and an emulsifier, which partitions at the oil-water interface, lowers interfacial tension, and sterically inhibits coalescence of the oil droplets. The emulsion is then added to a large volume of water to extract the organic solvent from the oil droplets. As the solvent leaves the droplet the polymer solidifies, encapsulating the drug. In this work, we describe the encapsulation of resveratrol, an amphiphilic polyphenol with anti-inflammatory and exercise mimetic properties, into poly(lactide-co-glycolide) (PLG) microspheres. A 3:1 ratio of dichloromethane to ethanol was required to dissolve PLG at 6% (wt/wt) and resveratrol at 10 mg/mL because resveratrol is insoluble in dichloromethane. The oil phase was added to water containing 1% (w/v) poly(vinyl alcohol) in a 1:7 ratio and suspended using a benchtop homogenizer. The emulsion was then added to a stirred beaker of water to extract the solvents and collect the particles. Interestingly, PLG particles made with resveratrol were irregular shaped, had ruffled surfaces, and were larger compared to particles made in the same manner except resveratrol was omitted. Particles lacking resveratrol exhibited smooth surfaces and spherical morphology typical of emulsions because this geometry minimizes interfacial tension between the oil and water. The degree of particle ruffling and expansion was resveratrol concentration dependent, with lower concentrations of resveratrol in the oil phase leading to particles with lower degrees of particle irregularities. Furthermore, we could modulate particle morphology using other polyesters such as polycaprolactone. Particle morphology was characterized with SEM, surface area was measured with BET, and material properties were studied with DSC and XRD. This presentation will elucidate the mechanism by which resveratrol modulates interfacial tension at the oil water interface during solvent extraction and how this leads to expanded particles with high surface area. We will also discuss methods to produce PLG particles with high resveratrol loading that do not exhibit irregular morphologies. Finally, we will present how particles with high surface area modulate adipose tissue function and macrophage phenotype when injected into white and brown subcutaneous fat pads in the mouse.