Abstract
As the blood–brain barrier (BBB) hinders efficient drug delivery to the brain, drug delivery via the intranasal pathway, bypassing the BBB, has received considerable attention. However, intranasal administration still has anatomical and physiological limitations, necessitating further solutions to enhance effectiveness. In this study, we used transcranial magnetic stimulation (TMS) on fluorescent magnetic nanoparticles (MNPs) of different sizes (50, 100, and 300 nm) to facilitate MNP’s transportation and delivery to the brain parenchyma. To validate this concept, anesthetized rats were intranasally injected with the MNPs, and TMS was applied to the center of the head. As the result, a two-fold increase in brain MNP delivery was achieved using TMS compared with passive intranasal administration. In addition, histological analysis that was performed to investigate the safety revealed no gross or microscopic damages to major organs caused by the nanoparticles. While future studies should establish the delivery conditions in humans, we expect an easy clinical translation in terms of device safety, similar to the use of conventional TMS. The strategy reported herein is the first critical step towards effective drug transportation to the brain.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This research was supported by the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (2022M3C1A3081294), National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A2C2005385 and 2022R1A2C2092821), and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1A6A1A03047902).
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All authors contributed intellectually to the research. Eunbi Ye and Eunkyoung Park designed this study. The experiments were performed by Eunbi Ye and supported by Eunseon Kim. Jung Eun Lee provided advices for the experiments. All results were analyzed by Eunbi Ye, who also prepared the manuscript. Sung-Min Park, Eunkyoung Park, and Seung Ho Yang reviewed the manuscript critically for its intellectual content. All authors have read and approved the manuscript.
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Ye, E., Park, E., Kim, E. et al. Transcranial application of magnetic pulses for improving brain drug delivery efficiency via intranasal injection of magnetic nanoparticles. Biomed. Eng. Lett. 13, 417–427 (2023). https://doi.org/10.1007/s13534-023-00272-0
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DOI: https://doi.org/10.1007/s13534-023-00272-0