28] pH-sensitive liposomes for delivery of macromolecules into cytoplasm of cultured cells

Abstract

Publisher Summary This chapter discusses different aspects of liposome cell interaction that inspired the development of acid-destabilized lipid vesicles, the strategies used in creating pH-sensitive liposomes, their characteristics in vitro, and their potential as cellular delivery vehicles. Methodology will be presented to allow the preparation and evaluation of pH-sensitive liposomes. This chapter discusses various hypotheses will be advanced to explain critical steps that determine the efficiency of cytoplasmic delivery by pH sensitive liposomes. Destabilization of pH-sensitive liposomes in close proximity to cellular membranes could result either in liposome-endosome fusion, or in a gross destabilization of the endosome membrane. Either event likely would lead to cytoplasmic delivery of liposome contents. Clearly, testing these hypotheses will provide the basis for further optimization of pH-sensitive liposomes for cytoplasmic delivery. Antibodies may also maintain the liposome and cellular membrane in close apposition during the process of pH-dependent destabilization, thus improving the likelihood that destabilization of the liposome will destabilize the enclosing endocytic vesicle membrane as well.