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

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^LOOP 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^LOOP effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fib

SUBMITTER: Bai X 

PROVIDER: S-EPMC11315999 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature