Ahl Patrick L
PLA Formulation Consulting LLC, Princeton, NJ 08540, USA.
Pharmaceutics. 2025 Sep 1;17(9):1148. doi: 10.3390/pharmaceutics17091148.
Using lipid nanocarriers to deliver the mRNA of a specific antigen to immune cells is a powerful innovative approach to rapidly develop new safe and effective vaccines. Understanding and optimizing the mixing process necessary for mRNA lipid nanoparticles (LNPs) is the focus of this review. The first objective is to review the fundamentals of microfluidic and turbulent fluid-mixing basics needed to understand the mixing process. The mRNA LNP self-assembly flash nanoprecipitation/self-assembly process will be discussed. Then, some important experimental nanoparticle studies which are the basis for the current understanding of microfluidic and turbulent mRNA LNP mixing process will be reviewed. Finally, the current commercially available LNP mixing technology will be summarized. There appears to be no universally "best" mixing process for formulating nanoparticles or mRNA LNPs. Both chaotic advection and turbulent flow microfluidic mixing devices, using the proper parameters for each device, will formulate similar mRNA LNP vaccines during development research. However, the low fluid output of microfluidic devices may not be practicable at higher fluid flow rates. Larger-scale turbulent mixing devices are more suitable for clinical-scale mRNA LNP production.
利用脂质纳米载体将特定抗原的mRNA递送至免疫细胞是快速开发新型安全有效疫苗的一种强大创新方法。理解和优化mRNA脂质纳米颗粒（LNP）所需的混合过程是本综述的重点。第一个目标是回顾理解混合过程所需的微流体和湍流流体混合基础的基本原理。将讨论mRNA LNP自组装闪蒸纳米沉淀/自组装过程。然后，将回顾一些重要的纳米颗粒实验研究，这些研究是当前理解微流体和湍流mRNA LNP混合过程的基础。最后，将总结当前市售的LNP混合技术。对于纳米颗粒或mRNA LNP的配方，似乎不存在普遍适用的“最佳”混合过程。在开发研究过程中，使用适合每种设备的适当参数，混沌平流和湍流微流体混合设备都将制备出类似的mRNA LNP疫苗。然而，微流体设备的低流体输出在较高流体流速下可能不可行。更大规模的湍流混合设备更适合临床规模的mRNA LNP生产。
