We are continuing to review publications related to mannosylated liposomes. This discussion will be updated with any pertinent information as we find it or whenever new information is published.
Mannose receptor binding is one of the oldest proposed mechanisms for liposome targeting through surface modification of the liposomes. The increasing number of both cell-surface-associated and soluble mannose-binding proteins that have since been discovered reveal the complexity of the mechanism(s) involved in enhanced uptake of mannosylated liposomes . Yet, several publications present convincing data on the ability of liposomes with various different conformations of surface bound mannose molecules to target mannose-receptor positive cells both in vitro and in vivo. Unfortunately, most of these proven formulations have not been applied to selective macrophage depletion by encapsulation of clodronate in these liposomes. The clodronate liposome field, in particular, has been plagued by the introduction of a liposome formulation prepared in the presence of p-aminophenyl mannose, but without covalently coupling this modified sugar to the liposome surface. The profusely cited reference to this liposome preparation claimed to target mannose-receptor positive cells in the brain as well as deliver liposome cargo across the blood-brain barrier. We find the data in this paper to be very weak and cannot confirm that the formulation was ever appropriately characterized with respect to the presence of mannose capable of targeting the liposome to mannose-binding proteins. While some stronger data suggesting that this formulation may target mannose-receptor positive cells has been published, others find no evidence of targeting by this formulation. We conclude that studies specifically designed to characterize and assess the targeting ability of this formulation are required to justify the use of this formulation in targeting mannose-receptor positive phagocytes. Until these studies are completed and published, we recommend that formulations containing covalently-anchored mannose and demonstrating the ability to selectively bind mannose receptors be utilized when experimental design calls for mannose receptor targeting.Many different mannosylated lipids have been synthesized which effectively display mannose residues on the surface of liposomes suitable for binding to mannose receptors as judged by Con A agglutination and competitive inhibition of mannose receptor binding by mannose or mannose-containing macromolecules. These demonstrations, however, are more difficult to interpret in vivobecause of the multiple mechanisms by which phagocyte uptake of mannosylated liposomes is enhanced. The structures of these mannosylated lipids are shown on this page along with a brief discussion of the published characterization and behavior of liposomes containing these derivatives. While the rationale for the design, synthesis and biophysical properties of these molecules may not seem directly applicable to clodronate liposome studies, there is a great deal of useful information in these papers on the rational design of surface-modified liposomes which will be invaluable when interpreting mannosylated clodronate liposome depletion data as well as when attempting to deplete specific mannose-receptor-positive phagocyte subsets.
For the complete post see here: http://www.clodrosome.com/other-info/mannosylated-liposomes/