Unlocking the potential of lyophilization as a stability improvement strategy for lipid-based drug delivery system: A review

Lipid-based drug delivery systems (LBDDS) have emerged as promising platforms to enhance the bioavailability of poorly water-soluble drugs. However, despite their advantages, lipid nanocarriers such as liposomes remain vulnerable to physical and chemical instability during storage, resulting in aggregation, leakage, and degradation of encapsulated drugs. Lyophilization, or freeze-drying, has been extensively explored as a stabilization strategy to improve the shelf life and structural integrity of lipid-based formulations. This review discusses the principles, processes, and applications of lyophilization in liposomal drug delivery. A comprehensive analysis highlights how the inclusion of cryo- and lyoprotectants, particularly disaccharides like sucrose and trehalose, preserves vesicle morphology, prevents fusion, and maintains encapsulation efficiency during freeze-drying and rehydration. Recent advances demonstrate that lyophilized liposomes can retain their nanoscale size, zeta potential, and controlled release properties over extended storage periods, supporting their clinical viability. Furthermore, studies confirm that optimized lyophilization protocols not only improve physicochemical stability but also preserve biological activity, enabling effective targeted drug delivery. Collectively, lyophilization represents a transformative approach to overcoming critical challenges associated with the long-term stability of lipid-based nanocarriers.