I joined the faculty at the CU School of Pharmacy in 1998, and my early work focused on the stability of lipid-DNA complexes during freezing, drying, and storage.  In attempting to assess “recovery” of these new pharmaceutical entities, I became interested in the mechanism by which they facilitated delivery to target cells after systemic delivery.  We soon recognized that the exposure of particles to serum proteins caused massive aggregation that resulted in accumulation in the lung.  In an attempt to avoid the use of PEGylated components, we used high cholesterol levels to impart resistance to protein-induced perturbations.  In addition to imparting stability, we documented that cholesterol forms phase-separated lipid domains within our particles that offer an optimal location for targeting ligands.  Our more recent work demonstrated that these particles were being avidly taken up by circulating immune cells that elicited a potent cytokine response upon intravenous injection.  After expending considerable effort attempting to evade the immune response (with little success), we have shifted our focus toward exploiting the immunogenicity of particles to limit off-target accumulation of nanomedicines and promote tumor regression.  For the past decade, we have also been studying exosomes as nature’s method of delivering nucleic acids to cells.  While our initial work aimed to hijack exosomes as a delivery vehicle, we have found little value in this approach.  In addition to these projects, my lab is constantly involved in multiple formulation studies (anticancer cream, eye drops, parenterals, ointments, injectable sustained release systems) that utilize small molecules to treat a variety of conditions.