Mechanisms and kinetics of liposome-cell interactions

Although the possibility of targeting drugs to specific tissues and cells, as well as facilitating their uptake and cytoplasmic delivery has rendered liposomes a versatile drug carrier system with numerous potential applications in medicine, the molecular mechanisms of liposome-cell interactions are not understood well. Here we have reviewed the early and current concepts of liposome-cell interactions, including possible liposome receptors. Uptake of liposomes by cells can be modified by the lipid composition, particularly by the inclusion of steric stabilizers such as PEG-conjugated lipids. Such modifications also alter the circulation time and biodistribution of liposomes, which can thus be tailored for particular applications. The intracellular fate of encapsulated molecules can be modified by the use of pH-sensitive liposomes which can also be sterically stabilized. Cationic liposomes that can undergo lipid mixing with cellular membranes can deliver complexed DNA to cells, but most likely via an endocytotic process. Kinetic analysis of liposome-cell interactions can elucidate the numbers of liposome receptors of several types and the corresponding binding constants. It is likely that liposomes bind to different cell surface receptors on different cells, and that they utilize more than one type of receptor on a particular cell. The kinetic analysis also provides the rate constants of endocytosis and the percentages of liposomes that are bound or endocytosed.