针对鼻子到大脑的药物输送
Haosheng Shen1, Nikhil Aggarwal1, Beiming Cui2
1NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National Centre for Engineering Biology (NCEB), Singapore, Singapore.
Cell
|February 6, 2025
概括
通过嗅觉表皮, 工程化植物乳杆菌 (Lp) 有效地向大脑输送治疗药物. 通过减少食欲和体重来治疗肥胖症.
科学领域:
- 神经科学
- 微生物学
- 药理学
背景情况:
- 通过嗅觉上皮层 (OE) 提供一种直接的药物输送途径.
- OE的解剖学和吸收限制阻碍了这种输送途径的可行性.
- 植物乳杆菌WCFS1 (Lp) 是一种具有天然OE亲和力的共生细菌.
研究的目的:
- 设计Lactobacillus plantarum (Lp) 作为一种针对大脑的药物输送的载体.
- 在肥胖的小鼠模型中评估工程Lp的治疗效果.
主要方法:
- 植物乳杆菌WCFS1被设计为释放OE中的有效载荷分子.
- 在一只小鼠模型中进行了鼻腔注射.
- 使用了食欲调节激素的重组生产和分泌.
- 评估了与肥胖相关的症状,包括食欲,体重,葡萄糖代谢和脂肪量.
主要成果:
- 工程Lp成功释放了OE中的有效载荷分子并将其运送到大脑.
- 在小鼠体内注射工程Lp显著降低了食欲和体重增加.
- 观察到改善的葡萄糖代谢和减少的脂肪沉积.
- 在预防肥胖方面,工程化Lp证明了治疗效果.
结论:
- 乳杆菌植物 (Lp) 可以有效地被设计为用于脑向治疗的鼻腔输送载体.
- 这种方法显示出开发新型治疗肥胖和相关代谢障碍的巨大潜力.
- 对Lp介导的大脑输送的进一步研究可能为神经和代谢疾病治疗开辟新的途径.
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