Melike Ongun, Abhijeet Girish Lokras, Saahil Baghel, Zhenning Shi, Signe Tandrup Schmidt, Henrik Franzyk, Thomas Rades, Federica Sebastiani, Aneesh Thakur, Camilla Foged
Design of inhalable mRNA therapeutics is promising, because local administration in the respiratory tract is minimally invasive and induces a local response. However, several challenges related to administration via inhalation and respiratory tract barriers have so far prevented the progress of inhaled mRNA therapeutics. Here, we investigated factors of importance for lipid nanoparticle (LNP)-mediated delivery of mRNA to the respiratory tract. We hypothesized that: (i) the PEG-lipid content is important for providing colloidal stability during aerosolization and for mucosal delivery, (ii) the PEG-lipid contentinfluences mRNA expression in the lungs, and (iii) the route of administration (nasal versus pulmonary) influences mRNA expression in the lungs...
March 16, 2024: European Journal of Pharmaceutics and Biopharmaceutics