RECEPTOR VERSUS NONRECEPTOR MEDIATED CLEARANCE OF LIPOSOMES

Numerous studies have appeared over the years dealing with liposome-ce ll interaction mechanisms, most of them performed under in vitro condi tions with isolated cell populations or cell lines. It is remarkable t hat, nonetheless, there hardly seem to exist established and generally accepted views on how precisely liposomes interact with cells and by what parameters this is influenced. In this article we will summarize and discuss the most relevant studies (in our opinion) on this matter in relation to in vivo conditions and with special attention to the re lation between scavenger, complement and PS receptors. Researchers in the field have long been aware of the interaction of liposomes with bl ood proteins and their potential involvement in the process of liposom e elimination from the blood circulation. A few of these 'opsonizing' proteins have been identified, but it is not clear to what extent each of them determines the fate of the liposome in the blood stream and h ow liposomal parameters such as size, charge and rigidity play a role in this process. We will include in this article our own recent observ ations on a thus far largely ignored class of such liposomal 'opsonins ', the apolipoproteins. This class of plasma proteins, which physiolog ically are instrumental in hepatic lipoprotein clearance and processin g, has been shown to contribute specifically to hepatocyte-mediated up take of liposomes. Separately, as opposed to the fate of plain liposom es, we briefly touch on the clearance of surface-modified liposomes, w hich are designed to actively target specific cells or tissues. Plasma proteins are not usually supposed to play a significant role in the c learance of such liposomes. We will summarize these studies and addres s in this connection the question of how plasma proteins may interfere with such active targeting attempts. (C) 1998 Elsevier Science B.V.