An
iron chelator of low water solubility,
HBED, has been encapsulated in the
lipid bilayers of unilamellar and multilamellar
liposomes. The effectiveness of
liposome-encapsulated
HBED for removing excess
iron burden from the RE system of the mouse liver (i.e., Kupffer cells) has been compared to that of the most commonly used
iron chelator, DF, a water-soluble
drug. We report the following: (1) At a single dose of 25 mg/kg,
HBED in
liposomes is more effective in removing excess
iron than free nonencapsulated
HBED. (2)
HBED is a more potent
iron chelator than DF; after a single dose of 25 mg/kg, about 25% of the originally injected
iron is excreted within 7 days from mice given
HBED either in small unilamellar or in large multilamellar
liposomes, whereas about 18% is excreted from mice given the same dose of
liposome-encapsulated DF. (3) Although the
iron burden is introduced into the Kupffer cells,
liposome-encapsulated
HBED promotes
iron excretion mainly via the bile and feces, whereas
liposome-encapsulated DF promotes
iron excretion through the kidney. (4) Cell fractionation studies show that encapsulation of
HBED in the
lipid bilayers of
liposomes does not alter the uptake pattern of
liposomes by the Kupffer and parenchymal cells of the liver; in other words, Kupffer cells are more effective in taking up large-sized multilamellar
liposomes while parenchymal cells take up small-sized
unilamellar liposomes more effectively. (5) Electron microscopic studies demonstrate that the liver biliary canaliculi are enlarged and filled with vesicular materials in mice given
liposome-encapsulated
HBED and that this condition does not occur in control mice or mice given
liposome-encapsulated DF. Our results have thus demonstrated that
liposomes could be very useful as injection vehicles for
metal chelators that are not readily soluble in water.
HBED is also demonstrated to be far superior to DF, the
iron chelator of choice for
therapy of transfusional
iron overload.