Targeted liposomal drug delivery: a nanoscience and biophysical perspective

Liposomes are a unique platform for drug delivery, and a number of liposomal formulations have already been commercialized. Doxil is a representative example, which uses PEGylated liposomes to load doxorubicin for cancer therapy. Its delivery relies on the enhanced permeability and retention (EPR) effect or passive targeting. Drug loading can be achieved using both standard liposomes and also those containing a solid core such as mesoporous silica and poly(lactide-co-glycolide) (PLGA). Developments have also been made on active targeted delivery using bioaffinity ligands such as small molecules, antibodies, peptides and aptamers. Compared to other types of nanoparticles, the surface of liposomes is fluid, allowing dynamic organization of targeting ligands to achieve optimal binding to cell surface receptors. This review article summarizes development of liposomal targeted drug delivery systems, with an emphasis on the biophysical properties of lipids. In both passive and active targeting, the effects of liposome size, charge, fluidity, rigidity, head-group chemistry and PEGylation are discussed along with recent examples. Most of the examples are focused on targeting tumors or cancer cells. Finally, a few examples of commercialized formulations are described, and some future research opportunities are discussed.