通过向大脑输送装载有塑体DNA编码血管素受体shRNA的纳米颗粒来降低血压
Richard Nii Lante Lamptey1, Chengwen Sun1, Jagdish Singh1
1Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA.
Molecular therapy. Nucleic acids
|June 3, 2024
概括
研究人员开发了新的脂质体,以传递向大脑 ангиотензин II 受体的遗传物质,有效降低高血压大鼠的血压. 这一突破为神经性高血压提供了一个有前途的新治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 生物技术是生物技术.
背景情况:
- 脑血管新素II活性升高是神经性高血压的主要驱动因素.
- 目前针对中央血管新素II活性的治疗方法由于传递挑战,无法在临床上转化.
研究的目的:
- 开发和评估双功能性脂质体,以有针对性地向大脑输送治疗剂.
- 评估这些脂质体在降低血管新生素II受体表达和降低神经性高血压的小鼠模型中降低血压方面的疗效.
主要方法:
- 使用薄膜水化和后插入方法合成了双功能性脂质体.
- 脂质体上装载着对抗血管激素II受体 (PEAS) 的短毛RNA编码的等离子体DNA.
- 在体外研究中评估了脂质体生物相容性和传递给大脑细胞,而在体内研究中使用自发高血压的老鼠进行血压监测.
主要成果:
- 合成的脂质体表现出一个阴离子表面电荷,平均尺寸为150nm,和>89%的PEAS捕获效率.
- 高效的输送到脑细胞导致>70%的受体表达减少在7天内.
- 与对照组相比,静脉注射给大鼠显著降低了超过30 mm Hg (p < 0.001) 的平均动脉压.
结论:
- 双功能性脂质体代表了一个可行的和有效的平台,用于针对大脑的核酸治疗药物.
- 这种方法显示出通过向中央血管新生素II活性来管理神经性高血压的显著治疗潜力.
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