Carbohydrate-mediated liposomal targeting and drug delivery

Abstract

The surface of the cell is rich in carbohydrate moieties attached to both membrane glycolipids and glycoproteins. These oligosaccharides constitute potential recognition sites for carbohydrate-mediated interactions between cells and drug carriers bearing suitable site-directing molecules. Liposomes constitute a potentially valuable type of drug carrier. The ability to incorporate various site-binding molecules into the liposomal surface leads to a wide range of delivery systems based on carbohydrate-mediated interactions. In this review the types of recognition site on the surface of mammalian cells are considered with regard to both their chemical composition and the physical constraints which might effect their recognition by drug carriers with site-directing groups. Of particular current interest are the cell surface carbohydrate-binding proteins (lectins) which have yet to be fully exploited as recognition sites for carrier systems. Potential liposomal drug carriers have been considered under a range of headings: glycolipid-bearing, glycoprotein-bearing, virus spike glycoprotein-bearing (the so-called ‘virosomes’), antibody-bearing immunoliposomes, lipopolysaccharide, polysaccharide-bearing and lectin-bearing. Examples of the applications of these various types of liposomes and their targeting to recognition sites on cells are reviewed. It is clear that while these systems could be of considerable value for the targeting of drugs, a great deal more work has been reported on the preparation, control and targeting of liposomal systems involving carbohydrate-mediated interactions than has been reported on their actual use for the delivery of specific drugs to cells. Carbohydrate-mediated drug delivery using liposomes is a very sophisticated approach which will not be easy to exploit without very considerable investment. At present, much of the technology required to exploit carbohydrate-mediated interactions in drug delivery is available and future progress will depend on a determination to use this technology to develop drug-carrying liposomal systems. The diversity of potential systems is large and the choice of liposomal system for targeting a drug to a particular cell type will have to be determined by balancing specificity of the liposomal carrier against ease of production.