关于混合因子如何控制RNA脂质纳米粒子配方中的多电解质-表面活性剂复合的机制性见解
Sophia R Dasaro1, Abhishek Singh2, Pavlos Vlachos2
1Department of Agricultural and Biological Engineering, Purdue University, 225 S. University St., West Lafayette, IN 47907, USA.
Journal of colloid and interface science
|August 25, 2024
概括
稳定的脂质纳米粒子 (LNP) 的形成需要精确的混合. 闪光纳米沉 (FNP) 显示,即使是微小的流量波动也会破坏LNP大小和RNA封装,强调在LNP生产中需要控制混合协议.
科学领域:
- 生物技术是生物技术.
- 材料科学 材料科学 材料科学
- 化学工程是化学工程的重要组成部分.
背景情况:
- 脂质纳米粒子 (LNP) 自组装对于核酸输送至关重要,由离子配对驱动.
- 目前的研究往往侧重于化学配方因素.
- 物理因素,如混合协议,不太了解,但对于可重复的LNP形成至关重要.
研究的目的:
- 机械地研究混合协议对LNP自组装的影响.
- 使用闪光纳米沉 (FNP) 来对混合参数进行受控和可重复的分析.
- 将模型系统的发现推广到RNA-LNP配方中.
主要方法:
- 使用闪光纳米沉 (FNP) 快速,可重复的混合多电解质-表面活性剂系统 (PSS/CTAB) 和RNA-LNP配方.
- 系统地改变关键的混合参数:总流量,相对体积流量和流量波动大小.
- 分析了由此产生的多电解质-表面活性化合物 (PESC) 和RNA-LNP,以测量尺寸和封装效率.
主要成果:
- 流动波动低至±5%,显著损害了PESC的形成.
- 与稳定流相比,在波动流下形成的RNA-LNP较大 (132.7 nm与75.6 nm),封装效率较低 (34.0%与82.8%相比).
- 不均的混合导致度梯度扰乱水和静电力对复杂化至关重要.
结论:
- 控制和稳定的混合对于可重复的脂质纳米粒子形成至关重要.
- 闪光纳米沉 (FNP) 是一个优化LNP制造流程的宝贵平台.
- 了解和控制物理混合参数为工业LNP生产提供了实际见解.
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