(174i) Curcumin-Loading Human Choroid Plexus Organoid-Derived Extracellular Vesicles to Alleviate Neuro-Inflammation

Neuroinflammation is a common symptom of aging and often caused by several components such as, overexpression of pro-inflammatory factors by the microglia. An increase in the production of these factors can have detrimental effects in neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and brain tumors. Curcumin is a natural polyphenol sourced from turmeric and is most reputable for its anti-inflammatory, antioxidant, and anticancer properties. Curcumin suppresses inflammation by blocking the nuclear transcription factor-kB, which is responsible for regulating tumor necrosis factor α, a mediator for inflammation. Several in vitro and in vivo studies have indicated that curcumin has various medicinal properties such as antioxidant, anti-carcinogenic, and anti-inflammatory. Despite all the benefits of curcumin, its clinical application has been hindered due to its low solubility and stability in vivo. A possible solution for this is loading curcumin into exosomes. The goal of this study is to determine the loading efficiency of curcumin into choroid plexus (ChP) organoid derived extracellular vesicles (EVs) using sonication, incubation, and freeze-thaw cycling. Preliminary data have been collected to determine the loading efficiency of loading curcumin into mesenchymal stem cell (MSC) and ChP organoid-derived isolated exosomes via sonication. This was done as proof of concept in order to examine the loading capabilities of curcumin, to develop an effective curcumin solution, and to test loading protocols. An average loading efficiency of 25.92% was determined, which is in line with previous studies show a loading efficiency of 8-30% for sonication. Additional trials will be conducted to determine the loading efficiency of incubation and freeze-thaw cycling. Finally, the curcumin-loaded exosomes will be introduced to cells that have been exposed to amyloid beta 42 oligomers, and the inflammatory response will be determined. This study has significance of design cell-free therapeutics to treat neural inflammation in various neurological disorders.