Liposome-cell interactions: In vitro discrimination of uptake mechanism and in vivo targeting strategies to mononuclear phagocytes

The interactions of liposomes with cells have been extensively studied to determine their potential use as vehicles for the delivery of drugs in vivo. Since intravenously administered liposomes are, for the most part, cleared by cells of the reticuloendothelial system (RES), considerable effort has been made to take advantage of this phenomenon rather than view it as an obstacle. Indeed, cells of the RES, in particular macrophages, have been shown to play a vital role in homeostasis and in host defence mechanisms against infection and neoplasia. In this article, we present an overview of liposome-cell interactions, with particular emphasis on the techniques used to monitor the interaction of liposomes with macrophages. Specifically, we discuss methodologies which can be used to differentiate between liposome-cell fusion, adsorption and endocytosis in vitro. In addition, we outline the various strategies that have been employed for both actively and passively targeting liposomes to macrophages in vivo. We also review the rationale and various techniques for designing liposomes for enhanced macrophage uptake, which, in certain cases, results in the selective release of liposome-entrapped compounds in situ.