Liposomas

REVIEW

Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential
Maria Laura Immordino Franco Dosio Luigi Cattel
Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Turin, Italy

Abstract: Among several promising new drug-delivery systems, liposomes represent an advanced technology to deliver active molecules to the siteof action, and at present several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes”) to “second-generation liposomes”, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using severalmolecules, such as glycolipids or sialic acid. A significant step in the development of longcirculating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol) (PEG) in liposome composition. The presence of PEG on the surface of the liposomal carrier has been shown to extend blood-circulation time while reducing mononuclear phagocyte system uptake (stealth liposomes). Thistechnology has resulted in a large number of liposome formulations encapsulating active molecules, with high target efficiency and activity. Further, by synthetic modification of the terminal PEG molecule, stealth liposomes can be actively targeted with monoclonal antibodies or ligands. This review focuses on stealth technology and summarizes pre-clinical and clinical data relating to the principalliposome formulations; it also discusses emerging trends of this promising technology. Keywords: liposomes, stealth liposomes, targeted liposomes, immunoliposomes

Introduction
Clinical medicine possesses an extremely broad range of drug molecules currently in use, and new drugs are added to the list every year. One of the main goals of any treatment employing xenobiotics is to increase thetherapeutic index of the drug while minimizing its side-effects. The clinical utility of most conventional chemotherapeutics is limited either by the inability to deliver therapeutic drug concentrations to the target tissues or by severe and harmful toxic effects on normal organs and tissues. Different approaches have been attempted to overcome these problems by providing “selective” delivery to theaffected area; the ideal solution would be to target the drug only to those organs, tissues, or cells affected by the disease. Selected carriers, such as molecular conjugates and colloidal particulates, can be suitable for this purpose. Colloidal particulates result from physical incorporation of the drug into a particulate colloidal system such as liposomes, niosomes, micro- and nano-spheres,erythrocytes, and polymeric and reverse micelles. Among these carriers, liposomes have been most studied. Their attraction lies in their composition, which makes them biocompatible and biodegradable. They consist of an aqueous core entrapped by one or more bilayers composed of natural or synthetic lipids. Liposomes composed of natural phospholipids are biologically inert and weakly immunogenic, andthey possess low intrinsic toxicity. Further, drugs with different lipophilicities can be encapsulated into liposomes: strongly lipophilic drugs are entrapped almost completely in the lipid
International Journal of Nanomedicine 2006:1(3) 297–315 © 2006 Dove Medical Press Limited. All rights reserved

Correspondence : Maria Laura Immordino Via Pietro Giuria 9, 10125, Torino, Italy Tel +39 0116707697 Fax +39 011 2367697 Email marialaura.immordino @ unito.it

297

Immordino et al

formulations: liposomes protect encapsulated molecules from degradation and can passively target tissues or organs that have a discontinuous endothelium, such as the liver, spleen, and bone marrow. On intravenous administration, liposomes are rapidly captured by the mononuclear phagocyte system (MPS) and...