This project aims to establish a collaboration aimed at developing locally-acting, injectable drug formulations for treating arthritis. In particular, we are interested in testing drugs that specifically target the endocannabinoid signaling system of inflammatory macrophages, which have been implicated in a variety of arthritic conditions. Ultimately, the goal is to develop and test new kinds of emulsions or solid microparticulate drug depot formulation that can be directly delivered into the joint to avoid any systemic side effects. We propose to test these formulations in animal models that exhibit the most relevant characteristics of arthritic joints (inflammation and pain). Following synthesis and physical characterization of the microparticulate drug formulation, we will probe how the stability/dissolution properties of the microparticles (as measured in vitro) are related to the observed in vivo efficacy and toxicity properties of the injected drug formulation. Subsequently, the efficacy and toxicity of the best formulation will be compared to the efficacy and side effects of the drug following administration via alternative delivery routes (transdermal or intraperitoneal injection).