New undisclosed project created on 2019-12-05 submitted by: University of Kansas Medical Center In: Kansas City, US
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Explaining The Mechanism of Clodronate Liposomes
Clodronate is not a toxic drug in itself and liposomes (if prepared of phosphatidylcholine and cholesterol) are not toxic either.
Free Clodronate will not easily pass phospholipid bilayers of liposomes and cell membranes but liposomes are eagerly swallowed by macrophages.
The implication is 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 (J. Immunol. Meth. 193: 93-99, 1996).
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ABOUT CLODRONATE LIPOSOMES
Clodronate liposomes are suitable for depleting macrophages. After administration, macrophages ingest and digest the phospholipid bilayers of the liposome, whereas clodronate will accumulate in the cell and eventually eliminate the macrophage by initiating its programmed cell death.
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