Back to Search Start Over

Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy.

Authors :
Bai, Xin
Chen, Qijing
Li, Fengqiao
Teng, Yilong
Tang, Maoping
Huang, Jia
Xu, Xiaoyang
Zhang, Xue-Qing
Source :
Nature Communications; 8/10/2024, Vol. 15 Issue 1, p1-18, 18p
Publication Year :
2024

Abstract

Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative "LOOP" platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08<superscript>LOOP</superscript> featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs. By incorporating mRNA encoding IL-11 single chain fragment variable (scFv), scFv@iLNP-HP08<superscript>LOOP</superscript> effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fibrosis. This formulation surpasses both inhaled and intravenously injected IL-11 scFv in inhibiting fibroblast activation and extracellular matrix deposition. The HP08<superscript>LOOP</superscript> system is also compatible with commercially available ALC0315 LNPs. Thus, the "LOOP" method presents a powerful platform for developing inhaled mRNA nanotherapeutics with potential for treating various respiratory diseases, including idiopathic pulmonary fibrosis. Inhaled lipid nanoparticles face several challenges when delivered to the lungs. Here, the authors show "LOOP"-optimized iLNP-HP08<superscript>LOOP</superscript> could withstand shear damage generated during nebulization process and be used to develop mRNA-mediated antibody therapy for treating idiopathic pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
178953226
Full Text :
https://doi.org/10.1038/s41467-024-51056-8