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The application and usefulness of resealed erythrocyte as a cell carrier of dexamethasone were studied in rabbits. The erythrocytes were loaded with water soluble dexamethasone sodium phosphate by hypotonic dilution and dialysis methods. During in vitro incubation at 37 degrees C, the level of dexamethasone held within the resealed according erythrocytes declined according to first-order function. About one half of the dexamethasone-loaded cells, when returned to circulation, disappeared within the first 24 h. However, the survival of the remaining cells in circulation followed zero order function and declined for 7-8 d after administration. The apparent half-life of the remaining erythrocytes in circulation was 8.27 d by the hypotonic dilution method and 12.8 d by the dialysis method. This indicated that the encapsulated drug had a much longer half-life than when free drug (t 1/2, beta = 3.61 +/- 0.69 h) was administered intravenously. Dexamethasone phosphate entrapped within cells was slowly released from the loaded cells into plasma in in vivo circulation. When the encapsulated cells were administered to rabbits, the rabbits were protected from inflammation (the capillary permeability response) caused by histamine for approximately 2 to 5 d after administration. However by day 10 the protection was slight. This anti-inflammatory effect agreed reasonably well with the in vivo survival of loaded erythrocytes. Therefore, the results indicated that resealed erythrocytes act as a slow release system in vivo.

Encapsulation of dexamethasone in rabbit erythrocytes, the disposition in circulation and anti-inflammatory effect.