Anionic lipids direct efficient microfluidic encapsulation of stable and functionally active proteins in lipid nanoparticles.

ABSTRACT: Because proteins do not efficiently pass through the plasma membrane, protein therapeutics are limited to target ligands located at the cell surface or in serum. Lipid nanoparticles can facilitate delivery of polar molecules across a membrane. We hypothesized that because most proteins are amphoteric ionizable polycations, proteins would associate with anionic lipids, enabling microfluidic chip assembly of stable EP-LNPs (Encapsulated Proteins in Lipid NanoParticles). Here, by employing anionic lipids we were able to efficiently load proteins into EP-LNPs at protein:lipid w:w ratios of 1:20. Several proteins with diverse molecular weights and isoelectric points were encapsulated at efficiencies of 70 75%-90% and remained packaged for several months. Proteins packaged in EP-LNPs efficiently

SUBMITTER: Ambati S 

PROVIDER: S-EPMC12553553 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature