(194ac) Evaluation of Microparticles Designed to Modify Adipocyte Endocrine Function

Obesity and its associated metabolic complications are on the rise and current therapies are insufficient. A hallmark of obesity is adipose tissue dysfunction characterized by its downregulation of adipokines that promote healthy metabolism and production of inflammatory cytokines that exacerbate disease. In effort to correct or direct adipose tissue function, we are developing biodegradable microparticles that modulate the endocrine function of adipocytes, the principal cell within the adipose tissue. Microparticles are composed of poly(lactide-co-glycolide) (PLG), which is FDA approved for several applications, and fabricated using a single emulsion/solvent evaporation technique. Treatment of 3T3-L1 or primary porcine adipocytes with PLG microparticles induces expression of adiponectin, an adipokine that promotes healthy metabolism and is downregulated during obesity. Interestingly, polystyrene microparticles with a similar size distribution downregulate adiponectin in the same cells, indicating the response is specific to PLG. This presentation will focus on our work to elucidate the physiochemical properties of PLG that elicit adiponectin production. By modulating PLG composition and microparticle production parameters (i.e., PLG concentration, homogenization speed, and surfactant formulation) we have developed a library of particles with varying composition, size, degradation rate, and surface charge. We will discuss the effects of these properties on adipocyte adiponectin expression and propose a mechanism of how we think the particles are working. Collectively, we expect these studies to elucidate how biomaterial-cell interactions modulate adipocyte function and lay the foundation for a microparticle based therapy for the treatment of obesity.