Sugar ligand-mediated drug delivery

Glycosylation modification of drug-delivery systems can improve their specific targeting and overcome the problems of wide distribution and serious side effects of drugs in vivo (1). At present, mannose, galactose and glucose are commonly used as active-targeting glycosyl ligands. Mannose, galactose and glucose have many active hydroxyl groups - they can covalently bind with the active groups of drug-delivery systems, such as amino and carboxyl groups. These sugars have the advantages of good biocompatibility, stability and low toxicity (2). Herein, the targeting mechanisms, synthesis methods and effects on the targeting characteristics of glycosylated drug-delivery system were reviewed. It would provide ideas and methods for the research of glycosylated drug-delivery system.

The modification methods of glycosylation

Lectin receptors and GLUT1-mediated targeted drug-delivery systems include glycosylation modification of drugs and carriers. Acetylation based on monosaccharide anomeric carboxyl protection and Maillard reaction between active amino group and reducing sugar (3) are the main reaction types of glycosylation modification in drug-delivery system. The aim is to protect the hydroxyl group of anomeric carbon of sugar ligand such as mannose, galactose and glucose by introducing an alkane chain-containing active halogenated group into anomeric carbon, so that malonic acid derivatives are reacted with active halogenated group and then covalently connected with the target drug-delivery system (Figure 1). Another modification method involves the Maillard reaction of drug-delivery system having active amino groups (chitosan, protein, liposome, etc.) with carbonyl groups of ring-opening reducing sugars, in other words, reductive amination (4). In this reaction, monosaccharides such as mannose, galactose and glucose are first prepared into ring-opening type, and then added to the drug-delivery system modified with amino groups. Sufficient reaction can result in the glycosylated drug-delivery system.

The modification with glucosyl group

Glucose can be protected its anomeric carbon by acetylation, active groups on anomeric carbon can be introduced, followed by reaction with targeted drugs after hydrolysis to prepare targeted drug-delivery systems. In addition, the conjugate of open-loop glucose and albumin can be synthesized directly by the Maillard reaction. The conjugate can be protected by esterification, then reacted with targeted drugs by introducing active reaction groups, or synthesized intermediates such as N-succinylglucosamine,...