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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Liposome and multiple emulsion formulations augment the anticalcifying efficacy of phosphocitrate in a cutaneous calcergy model.

The anticalcifying agent phosphocitrate was incorporated into phosphatidylcholine/cholesterol liposomes by reverse-phase evaporation. The compound was entrapped to the extent of 11.6% (mol mol-1 of lipid) and the liposomes exhibited prolonged retention of the compound when incubated with rat plasma. Phosphocitrate's ionic contribution in solution adversely influenced the encapsulation efficiency but improvements were made through ion-pairing with the quaternary ammonium detergent centrimide, or with the inclusion of stearylamine in the lipid phase. The liposomal dose that could be practically administered in-vivo was restricted to 2.5 mg phosphocitrate kg-1 day-1. The formulation of a multiple emulsion preparation of phosphocitrate, however, offered an alternative delivery mode permitting infrequent dosing to be successfully investigated. In a rat calcergy model, both vehicles effectively reduced the formation of induced subcutaneous calcified plaques at doses for which the phosphocitrate salt alone was inactive. The current formulations demonstrate that the therapeutic efficacy of phosphocitrate can be markedly improved through an appropriately designed drug delivery system, signalling a new approach for the future therapeutic application of this compound.[1]


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