Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
In recent years, the application of nanomaterials (NMs) is expanding. Although NM-based drug delivery carriers are expected to enhance drug transfer to the brain via the nose-to-brain pathway, the detailed pathway and hazards have not been understood. Therefore, in order to develop safe and effective drug delivery carriers to the brain, it is important to evaluate the kinetics of NMs. In this context, we focused on amorphous silica nanoparticle (nSP) which has been reported to be effective as a drug carrier. We investigated the intracellular uptake pathway in vitro and kinetics of nSP after the intranasal administration in vivo. The mouse microglial cell line MG6 were used in this study. Cells were exposed to fluorescent nSP with a particle size of 10 nm, 50 nm and 100 nm in diameter (nSP-10, -50 and -100). Uptake of nanoparticles were analyzed by confocal high content imaging system and flow cytometry. nSP10 was administered intranasally to mice, and sagittal sections of heads were observed by fluorescent microscopy. The fluorescence intensity of nSP10 taken up into MG6 was measured by flow cytometry, and results indicated that intracellular uptake of nSP10 was increased in a concentration-dependent manner. We further observed intracellular uptake of nSP10, 50 and 100 in MG6 by time-lapse analysis. Results indicated that nSP with smaller particle size was taken up into cells in early time point. Furthermore, when cells were treated with endocytosis inhibitors, the amount of nSP uptake was reduced. These results suggest that nSP might be taken up by endocytosis. In addition, in sagittal sections of heads, the fluorescence of nSP10 was observed in olfactory bulb, suggesting that nSP10 could reach the brain. Currently, we are analyzing protein expression changes in the mice brain after intranasal administration of nSP10, and try to evaluate the hazard of nSP10.
