Screening of Inhalable Nebulization Formulations and Elucidation of Aerosol Stabilization Mechanisms

Jinhyuk Jeong – Ph.D., Chungbuk National University, Republic of Korea; Jihyun Kang – Professor, Jeonbuk National University, Republic of Korea; Dongwook Kim – Professor, College of pharmacy, Wonkwang University, Republic of Korea; Chunwoong Park – Professor, Chungbuk National University, Republic of Korea

Introduction: Messenger RNA (mRNA)-loaded lipid nanoparticles (LNPs) are promising for pulmonary delivery because inhalation enables direct, localized treatment while minimizing systemic exposure. However, mesh-based nebulization subjects LNPs to mechanical and interfacial stresses, including shear forces and droplet coalescence, leading to nanoparticle deformation and mRNA leakage. Although device optimization can partially reduce these effects, physicochemical instability of LNPs persists during aerosolization. This study aimed to identify aerosol-stabilizing excipients and elucidate interfacial mechanisms for preserving LNP integrity.