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Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification
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Title: | Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification |
Authors: | Fukui, Takafumi Browse this author | Tateno, Hironao Browse this author | Nakamura, Takashi Browse this author →KAKEN DB | Yamada, Yuma Browse this author →KAKEN DB | Sato, Yusuke Browse this author →KAKEN DB | Iwasaki, Norimasa Browse this author →KAKEN DB | Harashima, Hideyoshi Browse this author →KAKEN DB | Kadoya, Ken Browse this author →KAKEN DB |
Keywords: | liposome | drug-delivery system | retrograde axonal transport | motor neuron | DRG |
Issue Date: | 15-Jun-2022 |
Publisher: | MDPI |
Journal Title: | International Journal of Molecular Sciences |
Volume: | 23 |
Issue: | 12 |
Start Page: | 6661 |
Publisher DOI: | 10.3390/ijms23126661 |
Abstract: | Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats. Liposomes in cell bodies were detected with infrared fluorescence of DiD conjugated to liposomes. Three days later, all nerve-administered liposomes were retrogradely transported to the spinal cord and DRGs, whereas only muscle-administered liposomes consisting of DSPC reached the spinal cord and DRGs. Modification with Cholera toxin B subunit improved the transport efficiency of liposomes to the spinal cord and DRGs from 4.5% to 17.3% and from 3.9% to 14.3% via nerve administration, and from 2.6% to 4.8% and from 2.3% to 4.1% via muscle administration, respectively. Modification with octa-arginine (R8) improved the transport efficiency via nerve administration but abolished the transport capability via muscle administration. These findings provide the initial data for the development of a novel DDS targeting the spinal cord and DRGs via peripheral administration. |
Rights: | https://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/86520 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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