Liposoma clodronate liposomes

Liposoma’s clodronate liposomes are artificial spheres consisting of concentric phospholipid bilayers encapsulating an aqueous PBS (phosphate buffered saline) solution containing clodronate. They have been used for the suppression of macrophage activity in various models of autoimmune diseases, transplantation, neurological disorders and gene therapy.

Free clodronate will not easily pass phospholipid bilayers of liposomes and cell membranes but liposomes are eagerly swallowed by macrophages. It is generally implied that clodronate, once delivered into phagocytic cells using liposomes as vehicles, will not escape from the cell. After disruption of the phospholipid bilayers of the liposomes under the influence of the lysosomal phospholipases in the macrophage, the drug, which is dissolved in the aqueous compartments between the liposomal bilayers, is released into the cell.

The clodronate is accumulated intracellularly, and after exceeding a threshold concentration, the cell is irreversibly damaged and dies by apoptosis. It is removed from circulation by the renal system. The approach can only be successful when the liposomes are able to reach the macrophages which have to be eliminated.

Clodronate liposomes are supplied as a suspension consisting of clodronate, phosphatidylcholine and cholesterol. The concentration of clodronate in the suspension is 5 mg per 1 mL. The liposomes are suspended in sterile phosphate buffered saline (10 mM Na₂HPO₄, 10 mM NaH₂PO₄ and >140 mM NaCl).