开发可喷雾的mRNA纳米颗粒,用于高效的肺部输送
Sri Sai Nikitha Kota1, Erik Moore2, Justin Tolman2
1Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska 68178, USA; Department of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
International journal of pharmaceutics
|August 30, 2025
概括
三聚酸纳米颗粒通过吸入有效地将信使RNA (mRNA) 输送到肺部. 这种新型的肺部药物输送系统有望改善细胞吸收和蛋白质表达.
科学领域:
- 生物技术
- 纳米医学
- 肺部医学
背景情况:
- 直接输送信使RNA (mRNA) 给肺部提供了一种革命性的非侵入性治疗方法.
- 目前的系统管理方法面临挑战和副作用,突出需要替代的交付系统.
研究的目的:
- 开发和描述可吸入的mRNA输送到肺部的奇多三聚酸盐 (CS-TPP) 纳米粒子.
- 评估CS-TPP纳米颗粒在封装mRNA中的效率及其适用于气溶.
主要方法:
- 使用具有成本效益的内部方法提取mRNA.
- 将mRNA纳入的CS-TPP纳米颗粒通过离子热制备,并以尺寸和封装效率进行特征化.
- 使用振动网状雾化器和下一代冲击器评估了空气动力学特性;肺细胞系中评估了细胞吸收和蛋白质表达 (A549,BEAS-2b).
主要成果:
- 吸入输送的最佳空气动力学直径为1-5μm.
- 在肺细胞系中观察到成功的细胞吸收和蛋白质表达.
- 免疫性研究显示了剂量依赖的细胞因子释放,表明潜在的治疗调节.
结论:
- CS-TPP纳米粒子是可吸入的mRNA肺部药物输送的可行平台.
- 开发的纳米颗粒证明了成功的气溶化,细胞吸收和蛋白质表达.
- 为了临床转换,需要进一步优化雾化和免疫性.
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