Intranasal Administration Enhances Size-Dependent Pulmonary Phagocytic Uptake of Poly (Lactic-Co-Glycolic Acid) Nanoparticles 9126

Abstract Description Background Nanoparticles exhibit distinct behaviors in the body based on their physicochemical properties and administration routes. The in vivo behavior of poly (lactic-co-glycolic acid) (PLGA) nanoparticles administered nasally is not well understood. This study investigates the in vivo behavior of PLGA nanoparticles through various routes. Methods PLGA-NH2 nanoparticles were synthesized in three sizes: small (294 nm), intermediate (522 nm), and large (850 nm) using an oil-in-water method. Uptake by murine macrophage RAW264.7 cells was assessed via fluorescence microscopy. For in vivo tracking, mice received nanoparticles with 89Zr-oxalate both intranasally and intravenously, and internalization by lung immune cells was examined. Results The uptake of small and large nanoparticles by RAW264.7 cells was similar, but phagocytosis inhibition reduced internalization of larger particles. Positron emission tomography showed that nasal delivery resulted in the highest pulmonary uptake, while intravenous administration led to significant accumulation in the liver and spleen. Nasal delivery of large nanoparticles enhanced uptake by myeloid immune cells compared to lymphoid cells, with dendritic cell uptake peaking initially and declining over time. Conclusion This study highlights the effectiveness of nasal delivery for PLGA nanoparticles and provides insights into nanomedicine. These findings may inform future clinical applications and improve therapeutic strategies. Funding Sources Defense Acquisition Program Administration [ADD-911255201] Topic Categories Vaccines and Immunotherapy (VAC)