The blood-brain barrier prevents the passage of most therapeutic drugs to the organ. The barrier is very selective in what’s allowed to pass through, but exosomes, the vesicles that pass chemical messages between cells, have a permanent green light. Researchers at University of North Carolina at Chapel Hill used this concept to ferry large therapeutic proteins across the blood-brain barrier to treat Parkinson’s disease.
The investigators at Chapel Hill used exosomes gathered from macrophage white blood cells and loaded them with catalase, a powerful antioxidant. Since Parkinson’s and many other neurological diseases cause inflammation in the brain, delivering an antioxidant to the site of inflammation may be therapeutic. The team tested the delivery system on mice by spraying the loaded exosomes into their noses, and showed that they passed through the blood-brain barrier carrying the cargo.
From the study abstract in Journal of Controlled Release:
Catalase 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 vitroand in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.
Study in Journal of Controlled Release: Exosomes as drug delivery vehicles for Parkinson’s disease therapy…
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