Abstract
Newly developed liposomes, containing amphipathic polyethylene glycol (PEG) derivatives, 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 is useful because of its ease of preparation, relatively low cost, controllability of molecular weight and linkability to lipids or protein including the antibody by a variety of methods. The presence of PEG reduces binding of serum protein, i.e. opsonins marking the liposome for clearance by MPS. PEG-liposome can take advantage of the EPR effect (enhanced permeability and retention effect) for efficient targeting binding in the tumor.
The blood clearance of immunoliposomes must be minimized in comparison with rate of extravasation in the tumor. As described above, PEG-liposomes offer the development of immunoliposomes with both long survival times in circulation and target recognition being retained in vivo. For the active targeting following the passive targeting to the solid tumor tissue, Fab' fragment of 21B2 antibody which is anti-human CEA or transferrin (TF) was conjugated to prepared the pendant type immunoliposome (Fab'-PEG-LP or TF-PEG-ILP). TF-PEG-LP could internalized into tumor cells with receptor mediated endocytosis following extravasation into tumor tissue. Such liposomal formulations should be useful for endocytotic internalization of plasmid DNA and other bioactive materials.
