(182aa) The Effect of Dispersed-Phase Solvent and Extraction Volume on Rosiglitazone Encapsulation in PLG Particles

Rosiglitazone (Rosi) is a potent synthetic PPAR gamma agonist that is FDA-approved for diabetes treatment. Its insulin-sensitizing effects are attributed to its ability to activate PPAR gamma in the adipose tissue; however, its use has been severely hampered by side effects such as cardiotoxicity in some patients. A potential method for decreasing these off-target effects is to encapsulate Rosi in a biodegradable drug delivery device and deliver it directly to the adipose tissue. We designed rosiglitazone encapsulated-poly(lactide-co-glycolide) (PLG) particles using an oil-in-water emulsion/solvent extraction technique. We determined the effect of dispersed phase solvent and extraction bath volume on Rosi particle loading, size, morphology and release kinetics. We also studied material properties using XRD, DSC and BET. We found that the choice of dispersed phase-solvent impacts drug loading and crystallinity of encapsulated drug. Furthermore, we found that the extraction bath volume can control the morphology of particles by controlling the speed at which dispersed-phase solvent is extracted from the oil droplets. This study establishes how fabrication parameters affect particle characteristics when encapsulating Rosi into PLG particles. Future studies will investigate these particles in the treatment of diet induced obesity and diabetes and elucidate how drug loading and particle surface morphology modulate adipose tissue function.