Impact of Lipid Nanoparticle Size and Charge on Lymph Node Transport and Distribution in Microfluidic Mixing

Lipid nanoparticles (LNPs) are crucial vehicles for drug delivery, particularly in vaccines and gene therapies. However, their transport dynamics within lymphatic systems remain poorly understood. This study investigates how LNP size and surface charge influence their transport and distribution to lymph nodes, using a microfluidic mixing platform that mimics interstitial flow. LNPs of varying diameters (30–150 nm) and zeta potentials (-30 mV to +30 mV) were synthesized and characterized. Microfluidic assays revealed size- and charge-dependent variations in lymph node targeting efficiency, with smaller, slightly negative LNPs demonstrating superior transport and retention. These findings offer critical insights for the rational design of LNPs for targeted lymphatic delivery.