Hydrogen-induced airway mucus barrier disruption enhances aerosolized RNA delivery to reverse pulmonary fibrosis Hydrogen as a drug delivery system assistant. If this strategy is valuable, then the new technologies here can all achieve pulmonary delivery of drugs, especially nanoparticle drugs, with the help of hydrogen. This is a very interesting finding and is also helpful for our understanding of the biophysical characteristics of hydrogen. Academic colleagues should read this paper carefully. The industry can also draw inspiration from this. Hydrogen may help drug delivery and may also be valuable for parts such as eyes and skin. It is of particular significance for the beauty industry.
Aerosolized RNA therapy is very suitable for the treatment of respiratory diseases, especially pulmonary fibrosis (PF); however, achieving effective delivery remains challenging. In this study, we demonstrated an efficient aerosol inhalation system that can achieve high levels of in vivo transfection efficiency in lung macrophages, thereby producing a durable response against pulmonary fibrosis. First, we established a nasal-only aerosol inhalation device that integrates a hydrogen replenishment system. This setup enables the precise delivery of lipid nanoparticles (LNPs) at a controllable low dose while delivering optimal concentrations of therapeutic hydrogen. We further developed a hybrid lipid nanoparticle (HNP) by hybridizing a pH-dependent charge-reversed lipid membrane with apoptotic T-cell membranes to enhance endosomal escape and trigger macrophage production of hepatocyte growth factor for lung repair. We demonstrated that hydrogen flow-induced shear stress disrupted the nanoparticle-mucus interaction and enhanced the deposition of aerosolized hybrid lipid nanoparticle/transforming growth factor β1 (TGFβ1) small interfering RNA (siRNA) at pulmonary fibrotic lesions, effectively blocking profibrotic signaling pathways and providing a clinically feasible strategy to combat pulmonary fibrosis.