Senior Scientist, Advanced Technologies Takeda Pharmaceutical Company Limited Cambridge, Massachusetts
Recently mRNA delivery using LNPs has become a hot topic in drug development. Although most LNPs reported have average particle size distribution (PSD) of ~60-100 nm, in applications like vaccines, larger particles may facilitate immune cell uptake. Manufacturing larger LNPs using microfluidic systems can be challenging due to process conditions changes such as alteration of aqueous to lipid phase ratio. Decreasing aqueous phase ratio relative to lipid/organic phase may lead to an increase in PSD but may lower encapsulation efficiency (%EE). In this study, we observed that higher lipid phase ratio led to increased PSD. Linear mRNA with large PSD was more susceptible to buffer effect evident in low %EE compared to circular mRNA. Buffer optimization improved %EE. Circular mRNA showed overall high %EE (>90%) with good PSD control carried through scale up steps. Similar formulation and process with 1.8x kb larger circular mRNAs maintained PSD and %EE control. The LNPs demonstrated particle stability in storage during the study period of 1 month.
Learning Objectives:
Participants will get a general overview of Lipid Nanoparticles
Participants will learn about process parameters to manipulate LNP particle size
The presentation will demonstrate effect of flow ratio on LNP particle size
The presentation will discuss influence of buffer strength on encapsulation efficiency
The session will explore and compare LNP particle stability between linear and circular mRNA cargo
