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Review
. 2006;1(3):297-315.

Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential

Maria Laura Immordino  1 , Franco Dosio, Luigi Cattel
Affiliations
Review

Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential

Maria Laura Immordino et al. Int J Nanomedicine. 2006.

Abstract

Among several promising new drug-delivery systems, liposomes represent an advanced technology to deliver active molecules to the site of 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 several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating 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). This technology 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 principal liposome formulations; it also discusses emerging trends of this promising technology.

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Figures

Figure 1
Figure 1
Increase in scientific research on liposomes: papers (vertical line) and reviews (horizontal line) published (total numbers on vertical axis). Data obtained from Ovid-Medline search keyword “liposomes”.
Figure 2
Figure 2
Chemical structures of distearoylphophatidylcholine (DSPC), distearoylphophatidylethanolamine after conjugation with poly-(ethylene glycol) (PEG) (DSPE-PEG) and DSPE-PEG linked with a targeting moiety.
Figure 3
Figure 3
Schematic diagrams of poly-(ethylene glycol) (PEG) configurations regimes (mushroom, brush and pancake) for polymer grafted to the surface of liposome bilayer.
Figure 4
Figure 4
Plasma values obtained from mice iv injected determined by 14C radioactivity associated to docetaxel in Tween 80 (crosses), docetaxel in conventional (black squares), and in PEGylated (gray squares) liposomes.
Figure 5
Figure 5
Schematic representation of conventional, stealth, targeted liposomes, and virosomes. Among different mechanism of intracellular uptake of liposomes, endocytosis of targeted liposomes is exemplified.
Figure 6
Figure 6
Chemical structures of the cationic lipids: dioleoylphophatidylethanolamine (DOPE), N-[1- dioleyloxy)propyl]-N,N,N-trimethylammonium (DOTMA) and 1,2-bis(oleoyloxy)-3-(trimethylammonio)p ropane (DOTAP).
Figure 7
Figure 7
Structure of dansylated cationic-poly(ethylene glycol)-lipid (CPL4) and schematic representation of the post-insertion method for the production of CPL4 liposomes (redrawn from Palmer et al 2003).
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