pH-Sensitive Liposomes as Tools for Cytoplasmic Delivery

Liposomes which were pH-sensitive were envisioned to release encapsulated drug as they passed through the regions of low pH. Liposomes, and in particular pH-sensitive liposomes, have been useftil tools for dissection of this important pathway. If transferrin conjugation directs liposomes to these sacs, pH-sensitive liposomes cannot be expected to release their contents or mediate cytoplasmic delivery of dye. Stabilization of Phosphatidyl ethanolamine (PE) into bilayers at neutral pH and construction of pH sensitive liposomes can be achieved by using one of several titratable, acidic lipids which are negatively charged at neutral pH values. The fact that DNA can be delivered when associated with the surface of pH-sensitive liposomes supports the idea that endosome destabilization may be involved. The ability to make pure PE liposomes is limited by the extreme conditions required for the feat and such liposomes are of limited usefulness due to their inherent instability.