(647e) Microparticles for the Delivery of Anti-Diabetic Drugs to the Adipose Tissue

Many drugs that show promise for metabolic diseases, such as obesity or diabetes, suffer from off-target effects and low bioavailability. Furthermore, efficacy may be decreased if the patient is unable or unwilling to follow the prescribed administration schedule. This presentation will focus on the development of a biodegradable microparticle delivery system for sustained, localized release of resveratrol to the adipose tissue. Resveratrol is a polyphenol with anti-diabetic properties that promote anti-inflammatory and anti-oxidant gene expression; however, the molecule is quickly metabolized in the blood and liver making it difficult to achieve therapeutic concentrations within adipose tissues. The microparticle delivery system was fabricated using a single emulsion/solvent evaporation technique to encapsulate resveratrol into poly(lactide-co-glycolide) (PLG), an FDA approved biodegradable polymer. We optimized drug encapsulation by varying the solvent, surfactant, homogenization speed, vessel geometry and resveratrol concentration in the organic phase. We then determined the effect of microparticle drug loading, size distribution, and morphology on the resveratrol release profile using UV-Vis spectroscopy, laser light scattering, and electron microscopy. To investigate the efficacy of drug delivery, we compared the effect of free resveratrol versus microparticles on gene expression, lipolysis rates and glucose uptake in 3T3-L1 adipocytes. Future work will address the translational potential of this system by investigating the effect of microparticle delivery to the inguinal and subscapular adipose tissues on glucose tolerance and adiposity in high fat diet fed mice. Collectively, we expect these studies to establish this microparticle delivery system as a means to modulate adipose tissue function as a potential treatment for diabetes.