在抗喘治疗中用于吸入输送的TAT装饰的siRNA复合体
Salvatore Emanuele Drago1, Marta Cabibbo1, Emanuela Fabiola Craparo1
1Lab of Biocompatible Polymers, Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, Palermo 90123, Italy.
概括
一种新型的共聚物有效地通过吸入传递siRNA用于喘管理. 这种配方形成了穿透粘液,进入细胞并减少炎症基因表达的纳米颗粒,提供了一个有前途的新疗法方法.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术纳米技术
- 呼吸系统医学 呼吸系统医学
背景情况:
- 喘管理需要有效的药物输送到肺部.
- siRNA传递系统面临着粘液透和细胞吸收方面的挑战.
- 开发可吸入的配方对于非侵入性喘治疗至关重要.
研究的目的:
- 设计和合成一种新型的可质子共聚合物,用于通过吸入输送siRNA.
- 为了使基于共聚合物的纳米颗粒具有细胞透的功能,以增强细胞吸收.
- 评估该配方在减少支气管上皮细胞中炎症基因表达的疗效.
主要方法:
- 从PHEA,bAPAE和PEG-MLB中合成一个质子性共聚合物.
- 用siRNA形成纳米大小的多复合体,并通过乙烯反应与TAT的功能化.
- 评估粘液扩散,细胞相容性,细胞吸收和基因沉默 (IL-8表达) 在体外.
- 将多重复合体封装成基于曼尼托尔的微粒,使用喷雾冷干燥来制造可吸入粉末.
主要成果:
- 纳米化的多复合体已经成功地用TAT形成和功能化.
- 装饰着TAT的多复合体表现出高效的粘液透和高细胞相容性.
- 多复合体被支气管上皮细胞有效地内化,导致IL-8基因表达减少.
- 喷雾冷干燥产生了含有siRNA载荷多重体的多孔,可吸入的微粒.
结论:
- 这种基于共聚合物的新型siRNA传递系统在吸入时是有效的,克服了粘液屏障.
- 具有TAT功能的多复合体促进支气管上皮细胞中的细胞吸收和基因沉默.
- 开发的可吸入干粉配方显示了喘管理的巨大潜力.
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