In the midst of many exciting developments in drug delivery technologies, nanotechnology holds promise for many new advances in targeted and controlled-release drug delivery platforms. Various drug nanoformulations have been developed to improve the therapeutic effect of drugs. Unfortunately, opsonization of drug-loaded synthetic nanoparticles in the bloodstream results in two distinct issues with drug nanoformulations: toxicity and rapid clearance by the mononuclear phagocyte system. In this respect, exosomes, nanosized vesicles secreted by a variety of cells, represent an important tool for both diagnostic and therapeutic purposes. Exosomes have the exceptional ability to interact with recipient cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. In light of this, we developed a new exosome-based delivery system for a potent antioxidant, catalase, to treat Parkinson’s disease (PD). The therapeutic protein was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100 - 200 nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.

Elena V. Batrakova was born in Moscow, USSR in 1960 and graduated with M.S. degree in chemistry from M.V. Lomonosov Moscow State University (MSU) in 1983. In 1987 she obtained Ph.D. in Polymer chemistry at the Department of Polymers, MSU, Russia. She is an Associate Professor of Pharmaceutical Sciences at the University of North Carolina at Chapel Hill, USA. The main focus of Dr. Batrakova’s group investigations is on the development of personalized drug delivery systems by loading therapeutics into living cells or exosomes released from these cells. We are taking advantage of white blood cells, monocytes and macrophages that can move toward an inflammation site, cross the blood-brain barrier, and release the preloaded drugs in the brain. We demonstrated that these “Trojan Horses” can attenuate inflammation and produce neuroprotection in mouse models of Parkinson’s disease. Several years ago, my interests expanded to the development of a novel class of vectors, genetically modified macrophages, which carry reporter and therapeutic genes to neural cells. These cells can accomplish ‘horizontal gene transfer” to the inflamed tissues, in particular to the brain. The separate investigations in my lab aim to use exosomes released from macrophages as drug delivery vehicles to treat pulmonary metastases and brain disorders. Overall, my group has published 87 papers and filed 20 US and foreign patents on the application of drug delivery systems of biologically active molecules. I have 8,259 unique citations with h-index: 45, and i10-index 66.