使用振动网状雾化器,通过肺输送siRNA脂质组和脂质纳米颗粒
Michael T Neary1, Lianne M Mulder2, Ciaran O Leime3
1SSPC, the SFI Research Centre for Pharmaceuticals, School of Pharmacy, University College Cork, Ireland; School of Pharmacy, University College Cork, Ireland.
概括
雾化将siRNA输送到肺部,但可能会损害纳米载体. 脂质纳米颗粒 (LNPs) 在雾化后表现出更好的siRNA传递和敲击比脂质复合体 (LPXs),突出显示纳米载体选择的重要性.
科学领域:
- 纳米医学是一种纳米医学.
- 药物运输 药物运输 药物运输
- 呼吸系统治疗药物 呼吸系统治疗药物
背景情况:
- 雾化是一种有前途的非侵入性方法,可以将小干扰RNA (siRNA) 输送到肺上皮.
- 然而,雾化过程可能会损害siRNA纳米载体的完整性,降低治疗疗效.
- 优化纳米载体配方对于有效的雾化siRNA输送至关重要.
研究的目的:
- 调查雾化,包括气溶液滴大小,对基于脂质的siRNA纳米载体的物理化学特性的影响.
- 为了比较不同纳米载体类型的稳定性和体外疗效,包括脂质组 (LPXs) 和脂质纳米粒子 (LNPs),在雾化后.
主要方法:
- 利用两个振动网状雾化器设备产生不同体积平均直径 (VMD) 的气溶.
- 对各种siRNA纳米载体配方的气溶液滴大小 (VMD) 和质量中介气动直径 (MMAD) 的特征.
- 在A549细胞中评估了siRNA封装效率,聚合,细胞活力和基因沉默 (火 luciferase knockdown).
主要成果:
- 在不同纳米载体类型中实现了一致的气溶液滴大小分布 (3.564.89μm).
- 脂质纳米粒子 (LNPs) 在雾化后表现出降低的siRNA封装效率.
- 脂质复合物 (LPX) 显示聚合,而LNP在体外表现出更高的基因沉默疗效 (高达93%),与PEGylated LPX (高达30%) 相比.
结论:
- 雾化可以产生具有适合肺部沉积的一致滴状大小的气溶.
- 纳米载体的选择显著影响稳定性和雾化后siRNA传递效率.
- 脂质纳米颗粒 (LNPs) 在雾化siRNA疗法中表现优于脂质复合剂 (LPXs),需要进一步研究.
相关概念视频
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...