Exosomes as Drug Delivery Vehicles for Parkinson’s Disease Therapy
By Matthew J. Haney, N. Klyachko, Yuling Zhao, Richa Gupta, E. Plotnikova, Zhijian He, Tejash T. Patel, A. Piroyan, Marina Sokolsky, A. Kabanov and 1 more. Journal of Controlled Release, 2015
1,744 citations recorded by the source corpus.
Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson’s disease (PD). 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 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.
Subfields: Molecular Biology, Pharmaceutical Science
View Paper: https://www.semanticscholar.org/paper/4c8cd05a3d077b7a59dade1c06ba2f131f0233a8
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Citations in the corpus
- Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment (2018, positive): “…brain of mice we con fi rmed the attenuation of ROS-triggered neuroin fl ammation by designer exosomes containing the catalase cargo by pro fi ling the expression levels of several markers (GFAP 28, 43 – 45 , Iba1 45, 46 , TNF α 44, 47 , CD11b 28 ) associated with neuroin fl ammation in the brain (Fig.”
- The Smart Drug Delivery System and Its Clinical Potential (2016, background): “For instance, Batrakova and coworkers have developed a novel exosome-based delivery system as catalase-loaded exosomes (exoCAT) to treat Parkinson's disease (PD) [179].”
- The biology, function, and biomedical applications of exosomes (2020, positive): “Macrophagederived exosomes loaded with catalase showed therapeutic benefit (neuroprotective effect) when administered intranasally in amousemodel of PD (232).”
- The exosome journey: from biogenesis to uptake and intracellular signalling (2021, background): “Production of engineered exosomes is an active research field, which fosters assessment of various therapeutic cargoes, enhancement of target selectivity and optimisation of manufacturing [17, 18].”
- Development of Exosome-encapsulated Paclitaxel to Overcome MDR in Cancer cells (2015, positive): “7 cells cultured in exosome-depleted media using the ExoQuick-TCTM Kit (System BioSciences; Mountain View, CA) and characterized by Nanoparticle Tracking Analysis (NTA), Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM) and Western Blot Analysis as described previously (29).”
- Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications (2020, neutral): “105 The method is easy to operate, highly reproducible, and does not affect the integrity of exosome membrane structure, but the loading efficiency is low, and a large number of therapeutic agents are needed.”