Critical quality attributes of lipid nanoparticles and in vivo fate

Lipid nanoparticles (LNPs) have emerged as versatile carriers for the delivery of genetic medicines and small-molecule drugs, offering desired benefits for therapeutic applications. Optimization of the treatment efficacy of nanocarriers necessitates a thorough understanding of the connection between pharmacokinetics and physicochemical properties. This review consolidates scientific efforts to elucidate how LNP's physicochemical attributes influence their <i>in vivo</i> fate, emphasizing particle size and shape, surface electric potential and ligand-binding chemistry. By examining the interplay between LNPs and biological barriers across various administration routes, this review provides insights into tailoring LNP properties for optimal delivery and reduced off-target effects. Recommendations for future research are provided to advance the study of LNP <i>in vivo</i> behaviors and offer a practical framework for optimizing <i>in vivo</i> performance through product design parameters.