Lupus Therapy using Nanoparticulate Drug Delivery

Lupus is a life-long, debilitating disease caused by the abnormal activation of the immune system against the body. This presentation describes the design and use of a novel, nanogel drug delivery system that can be used for treatment. Nanogels consist of a lipid exterior and gel-like interior that encapsulates the drug mycophenolic acid, an immunosuppressant. The in vivo efficacy of nanoparticles was evaluated in a lupus-prone mouse model, and significantly extended the median survival time by approximately 3 months with concomitant delay in the onset and severity of clinically-relevant markers of lupus. Nanogels provided better therapeutic efficacy than the conventional administration of drug solubilized in buffer by localizing to immune cell subsets that participate in lupus pathology and attenuating inflammation. Finally, the use of an alternative and commonly used polymer for formulating nanoparticles, poly(lactic-co-glycolic acid) (PLGA), was compared and found to be less efficacious due to its less efficient uptake by dendritic cells. These findings demonstrate the potential feasibility and design considerations of using nanoparticle-based therapeutic immunosuppression for lupus and other autoimmune diseases.