INTERACTIONS OF LIPOSOMES AND LIPID-BASED CARRIER SYSTEMS WITH BLOOD PROTEINS - RELATION TO CLEARANCE BEHAVIOR IN-VIVO

Liposomes and lipid-based drug delivery systems have been used extensi vely over the last decade to improve the pharmacological and therapeut ic activity of a wide variety of drugs. More recently, this class of c arrier systems has been used for the delivery of relatively large DNA and RNA-based drugs, including plasmids, antisense oligonucleotides an d ribozymes. Despite recent successes in prolonging the circulation ti mes of liposomes, virtually all lipid compositions studied to date are removed from the plasma compartment within 24h after administration b y the cells and tissues of the reticuloendothelial system (RES). Plasm a proteins have long been thought to play a critical role in this proc ess but only a few efforts were made to evaluate the relevant importan ce of plasma protein-liposome interactions in the clearance process. S trategies to increase the bioavailability of liposomal drugs have incl uded altering lipid compositions and charge, increasing lipid doses, a nd incorporating surface coatings. All of these modifications can infl uence membrane-protein interactions. In this article, we will focus on our experiences with liposome-blood protein interactions and how alte rations in the chemical and physical properties of the carrier system influence the interactions with blood proteins and circulation times. (C) 1998 Elsevier Science B.V.