Stability-preserving post-processing of mRNA-lipid nanoparticles utilizing a scalable ion concentration polarization...

Lipid nanoparticles (LNPs) have emerged as key vehicles for mRNA delivery. However, their physicochemical fragility during post-processing remains a critical bottleneck for clinical translation. In this paper, we present an ion concentration polarization (ICP)-based concentration strategy that enables the rapid, gentle, and selective enrichment of mRNA-LNPs. This process preserves essential physicochemical properties, including particle size (<80 nm), low polydispersity (PDI <0.2), and high encapsulation efficiency (>94 %), and maintains functional bioactivity, as demonstrated by protein expression in cell-based assays. Compared with conventional tangential flow filtration (TFF), the ICP-based method minimizes structural disruption and dilution loss, and its inherently modular and scalable design supports parallelized architectures for increased throughput. These results establish ICP-based concentration as a stability- and functionality-preserving post-processing approach with a strong potential for integration into the continuous manufacturing of next-generation RNA therapeutics.