RNA Lipid Nanoparticles Stabilized During Nebulization Through Excipient Selection

Abstract

Nebulization of lipid nanoparticles (LNPs) has demonstrated great potential for the treatment of various pulmonary disorders via therapeutic RNA delivery. However, during the nebulization process, LNPs are subjected to high shear forces that result in particle destabilization and consequent loss of cargo. Here, we provide a generalizable approach to stabilize LNPs by adjusting the nebulization buffer composition. We investigated the effect of buffer composition on nanoparticle size, RNA encapsulation efficiency, and LNP material recovery. We found that pH 5.0 citrate buffer reduces the loss of encapsulated RNA, poloxamer 188 maintains nanoparticle size and improves recovery, and glucose is important for an iso-osmotic solution. RNA encapsulated in nebulized LNPs maintained bioactivity as demonstrated with cellular uptake and functional siRNA delivery to Vero cells expressing nano luciferase. Together, this work shows a versatile strategy for the delivery of inhalable LNP-based RNA therapies.

Supplementary files

Article information

Article type
Paper
Submitted
12 Dec 2024
Accepted
21 May 2025
First published
03 Jun 2025
This article is Open Access
Creative Commons BY-NC license

Nanoscale Adv., 2025, Accepted Manuscript

RNA Lipid Nanoparticles Stabilized During Nebulization Through Excipient Selection

K. V. Slaughter, D. Isaacs-Bernal, E. N. Donders, S. Wang, S. G. Sabbah, X. Li, M. Dang, I. M. M. Jackiw, K. Y.T. Chan, P. R. Cullis and M. S. Shoichet, Nanoscale Adv., 2025, Accepted Manuscript , DOI: 10.1039/D4NA01034E

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