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Advanced $\"Elsevier\"$ Journal of Pharmacological and Toxicological MethodsVolume 27, Issue 3, May 1992, Pages 185-189 $\"Journal$ Efficient clodronate entrapment within multilamellar and unilamellar liposomesAuthor links open overlay panelWilliam G.LoveJeremy P.Camilleri

Bryan D.Williams

Show morehttps://doi.org/10.1016/1056-8719(92)90039-4Get rights and contentAbstract

Clodronate (dichloromethylene bisphosphonate) encapsulated within liposomes and adminestered intravenously eliminates resident macrophages within the liver and spheen. Macrophage depletion in the rat requires 20 mg of the encapsulated drug, and so far this has only been achieved using large multilamellar vesicles (MLV). Recent studies have shown that small unilamellar vesicles (SUV) when injected intravenously accumulate at inflamed joint sites in both animal models of arthritis and patients with rheumatoid arthritis; multilamellar vesicles were not able to do so. If phagocytic cells, such as macrophages, are responsible for SUV sequestration, then SUV containing clodronate may be targeted to the inflamed joint and may eliminate the macrophage population leading to reduction in the state of inflammation. We have adapted an existing technique to radiolabel clodronate with 99mTechnetium to use as a tracer to determine its encapsulation within liposomes, a technique that has advantages over other current methods. We have achieved a high-encapsulation efficiency of the drug within MLV and produce SUV containing sufficient clodronate to deplete macrophages in rats in a small enough volume to administer it intravenously as a single dose.

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