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RNA lipid nanoparticles stabilized during nebulization through excipient selection

delete2025-07-28
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OA
AI
K
Kai V. Slaughter
D
Daniela Isaacs-Bernal
E
Eric N. Donders
S
Siming Wang
S
Sami G. Sabbah
X
Xiang Li
M
Mickael Dang
I
Isaac M. Jackiw
K
Karen Y. T. Chan
P
Pieter R. Cullis
M
Molly S. Shoichet *
DOI：10.1039/D4NA01034Edelete
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Abstract

Abstract

En 中文
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.
Keywords:
lipid nanoparticles
nebulization
RNA delivery
siRNA
stabilization

Journal

Nanoscale Advances cover
Nanoscale Advances
IF:
4.6
Papers:
853
Citations:
1.5W

Organization

No organization information available