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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
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.
Type: article
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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