Abstract
The current status of the passive targeting by the newly developed polyethyleneglycol coated liposome (PEG-liposome) was described in this review. Liposomes have demonstrated considerable promise as a carrier for the delivery of drugs in vivo. However, one of the drawback is that ordinary liposomes intravenously injected into animals are rapidly removed from the blood circulation by uptake primarily in the cells of reticuloendothelial system (RES). It has been found that PEG-liposome are not readily taken up by the macrophages in the RES and hence stay in the circulation for a relatively long period of time. PEG-liposome is called STEALTH® liposome. Pharmacokinetic analysis and therapeutic studies with tumor bearing mice revealed that PEG-liposomes with an average diameter of 100-200 nm were accumulated efficiently in tumor tissue. Due to the capillary permeability of the endothelial barrier in newly vascularized tumors is significantly greater than that of normal tissues, PEG-liposomes could extravasate from blood circulation to tumor tissue. Results from clinical studies with doxorubicin encapsulated into PEG-liposomes (DOXIL®) in AIDS-related Kaposi's sarcoma revealed an increased therapeutic efficacy compared to free-drug. PEG-liposomes offer the development of immunoliposomes with both long survival times in circulation and target recognition being retained in vivo. A new type of long-circulating immunoliposome, which was PEG-immunoliposome attached antibody at the distal end of PEG chain, so called the pendant type immunoliposome, was designed. For targeting to the solid tumor tissue, Fab' fragment of 21B2 antibody which is and human CEA or transferrin (TF) was conjugated to prepared the pendant type immunoliposome (Fab'-PEG-ILP or TF-PEG-ILP, respectively). Both immunoliposomes showed the low RES uptake and the long circulation time, and resulted in enhanced accumulation of the liposomes in the solid tumor. TF-PEG-ILP could internalize into tumor cells with receptor mediated endocytosis following extravasation into tumor tissue. The pendant type immunoliposome can escape from the gaps between adjacent endothelial cells and openings at the vessel termini during tumor angiogenesis by passive convective transport much rather than ligand directed targeting. Targeting to tumor tissue with the pendant type immunoliposome is particularly important for many highly toxic anticancer drugs for cancer chemotherapy. An ultimate goal of pendant type immunoliposome is the incorporation of a fusogenic molecule that would induce fusion of liposome following their binding to the target cells or their internalization by endocytosis. Such liposomal formulations should be useful for endocytotic internalization of plasmid DNA and other bioactive materials.
