Therapeutic opportunities for targeted liposomal drug delivery

One way to increase the therapeutic index of drugs such as anticancer drugs, which have low therapeutic indices would be by specifically targeting the drugs to the diseased cells. This can be accomplished by associating the drugs with liposomes and coupling a targeting antibody or ligand to the liposome surface. A variety of coupling methods can be used to attach antibodies or ligands to the liposomes, and, to date, the best targeting results have been obtained when the targeting moiety is attached at the terminus of a hydrophillic polymer such as polyethylene glycol (PEG). Targeted liposomes have been demonstrated to have specific binding and increased cytotoxicity to cells in vitro compared to non-targeted liposomes. The best therapeutic results in vivo have been obtained to date when the liposomes are targeted to cells easily accessible within the vasculature, or to micrometastatic cells. Treatment of more advanced solid tumours with targeted liposomes presents a challenge to overcome the 'binding site barrier' at the tumour surface. Evidence is accumulating that targeting to internalizing receptors is more successful than targeting to non-internalizing receptors.