Issue 7, 2024

Ionic liquid-coated lipid nanoparticles increase siRNA uptake into CNS targets

Abstract

Lipidoid nanoparticles (LNPs) have transformed the field of drug delivery and are clinically used for the delivery of nucleic acids to liver and muscle targets. Post-intravenous administration, LNPs are naturally directed to the liver due to the adsorption of plasma proteins like apolipoprotein E. In the present work, we have re-engineered LNPs with ionic liquids (ILs) to reduce plasma protein adsorption and potentially increase the accumulation of LNPs in hard-to-deliver central nervous system (CNS) targets such as brain endothelial cells (BECs) and neurons. We have developed two approaches to re-engineer LNPs using a choline trans-2-hexenoate IL: first, we have optimized an IL-coating process using the standard LNP formulation and in the second approach, we have incorporated ILs into the LNPs by replacing the PEG-lipid component in the standard formulation using ILs. IL-coated as well as IL-incorporated LNPs were colloidally stable with morphologies similar to the standard LNPs. IL-coated LNPs showed superior uptake into mouse BECs and neurons and demonstrated reduced mouse plasma protein adsorption compared to the standard LNPs. Overall, our results (1) demonstrate the feasibility of re-engineering the clinically approved LNP platform with highly tunable biomaterials like ILs for the delivery of therapeutics to CNS targets like BECs and neurons and (2) suggest that the surface properties of LNPs play a critical role in altering their affinity to and uptake into hard-to-deliver cell types.

Graphical abstract: Ionic liquid-coated lipid nanoparticles increase siRNA uptake into CNS targets

Supplementary files

Article information

Article type
Paper
Submitted
28 aug 2023
Accepted
05 dec 2023
First published
05 dec 2023
This article is Open Access
Creative Commons BY-NC license

Nanoscale Adv., 2024,6, 1853-1873

Ionic liquid-coated lipid nanoparticles increase siRNA uptake into CNS targets

P. Khare, S. X. Edgecomb, C. M. Hamadani, J. F. Conway, E. E. L. Tanner and D. S Manickam, Nanoscale Adv., 2024, 6, 1853 DOI: 10.1039/D3NA00699A

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