Abstract
Lipid nanoparticles (LNPs) have emerged as clinically validated drug delivery vehicles, as demonstrated by the successful deployment of COVID-19 mRNA vaccines (Comirnaty and Spikevax) and siRNA therpy (Patisiran). Building on these achievements, we investigated the functional roles of free polyethylene glycol (PEG) molecules in optimizing LNP performance. This study focused on enhancing mucus penetration capability and maintaining storage stability under various storage conditions. We found PEG molecules (MW 400-6000 Da) significantly improved LNP penetrate through mucosal barriers, with PEG 2000 demonstrating optimal penetration efficiency. Stability assessments showed that LNPs remained stable in PEG media at -20 °C for 4 weeks. However, none of the tested PEG formulations prevented LNPs aggregation during lyophilization.