Improving Drug Entrapment Efficiency and Eliminating Free, Unloaded Drug Residues: A Review of Two Challenges with Liposomal Drug Delivery Systems

and the desired characteristics of the final formulation. However, these products face two significant challenges: the presence of free, nonencapsulated drug molecules, which must often be removed, and limited drug-loading efficiency. Currently, no universal method exists to address either issue fully. This review aims to provide a comprehensive overview of strategies to enhance drug entrapment and remove free, non-encapsulated drug from liposomal formulations, to compare the advantages and limitations of current methods, and to identify remaining knowledge gaps to guide future research and formulation design. To this end, the first section describes drug loading methods, followed by purification techniques, with an emphasis on recently developed approaches and their specific benefits and drawbacks.