Engineering the biophysical properties of lipid nanostructures for drug delivery

The physical properties of drug delivery vehicles are important for the development of effective and targeted treatment options for human disease. In this review, we elucidate the role of the fundamental physical properties such as size, charge, elasticity, curvature, fluidity, and asymmetry in optimizing lipid-based drug delivery systems. These properties significantly influence the performance of such drug delivery vehicles in overcoming biological barriers, minimizing clearance, and improving cellular uptake. The optimization of physical properties is important in bridging the translational gap and achieving consistent clinical outcomes. By focusing on the fundamental physical properties, we also provide a comprehensive review that identifies remaining knowledge gaps and guides future development of lipid-based nanocarriers. This Review explores the role of fundamental physical properties, such as size, charge, elasticity, curvature, fluidity, and asymmetry, on optimizing lipid-based drug delivery systems. Knowledge gaps and guidance for the future development of lipid-based nanocarriers are also discussed.