期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms23126661
关键词
liposome; drug-delivery system; retrograde axonal transport; motor neuron; DRG
资金
- General Insurance Association of Japan [JP21H03558]
- Japan Agency for Medical Research and Development [JP21gm6210004]
- Kobayashi Foundation
- SEI Group CSR Foundation
This study investigated the potential of liposomes as an efficient drug-delivery system for treating disorders of the central nervous system. By optimizing the liposomes and conducting experiments in a rat model, the study confirmed successful retrograde transport to the spinal cord and dorsal root ganglia. Modifying the liposomes with different substances improved their transport efficiency, providing valuable insights for the future development of novel DDS targeting the CNS.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据