Mannose receptor targeting by mannosylated liposomes has been demonstrated for a variety of mannosylated lipid conjugates in a variety of liposome morphologies and compositions in several different in vitro and in vivo models. There are several publications using a hydrophobic derivative of mannose (4-aminophenyl α-D-mannopyranoside) rather than using a mannosylated lipid in clodronate liposomes. This is mainly due to the high cost and complexity of synthesizing and conjugating mannose to lipid. 4-aminophenyl α-D-mannopyranoside is commercially available and far less expensive than synthesizing mannose conjugated lipid.

Why mannose? Mannose is one of the carbohydrate components of many bacterial and viral cell surfaces; therefore, the ever-efficient, highly redundant immune system has evolved multiple mechanisms for identifying pathogens based on mannose recognition. The animal and plant kingdoms likewise utilize carbohydrate recognition signaling mechanisms including mannose residues. Many publications evaluate other carbohydrates as targeting mechanisms for various cell types, however mannose targeting to phagocytes appears to be one of the more specific mechanisms identified to date. Mammalian cell surface identification molecules based on mannose binding, such as the ICAM family of leukocyte adhesion molecules, target the SIGN family of mannose receptors to accomplish self-recognition in vivo.

A well-known and cited study by Umezawa & Eto [1] demonstrates that liposomes containing aminophenyl mannoside were most efficiently incorporated into the mouse brain across the blood brain barrier. The radiolabeled liposomes bearing aminophenyl