The bioavailability and pharmacodynamics of liposomeencapsulated chemotherapeutic drugs must be considered in developing these delivery systems. To take advantage of the EPR effect, liposomes need to have long half-lives so that the drug stays within the carrier as long as possible in blood circulation until it accumulates in diseased tissues [81] . Once liposomes are localized to a solid tumor, the drug they contain must be released and become bioavailable at a rate remains therapeutically effective for a period of time. The rate of active drug's release into tumor cells, not the total drug concentration in the tumor tissues, is critical for measuring the actual bioavailability of the liposomal drug [16] . Some targeting liposomes have not been found to have greater therapeutic efficacy than passive liposomal drugs, possibly because the lack of internalizing ligands does not give the drug greater access inside tumor cells [82, 83] . Drug delivery can be further enhanced if the liposome-attached ligands bind selectively to internalizing antigens which would help increase the concentration of drugs inside tumor or tumor-associated endothelial cells resulting in higher drug concentration inside the cells [13, 15, 84, 85] . This binding to internalizing antigens by ligands can induce receptor-mediated endocytosis of liposomes into endosome compartments with low pH, where the liposomes break down and release the encapsulated drug into the intracellular space ( Figure 3 ). These steps lead to higher intracellular drug concentration and greater destruction or inhibition of tumor cells. Studies have confirmed greater cytotoxic effects produced by liposomes with peptides that target internalizing antigens through enhanced specificity and improved drug bioavailability [2, 16] .