Effect of administration route on the selective lymphatic delivery of cyclosporin A by lipid-surfactant mixed micelles.

Abstract

The absorption and lymphatic delivery of a new immunosuppressive drug, cyclosporin A (CsA), with the aid of lipid surfactant mixed micelles (MM) system using different administration routes were studied in the thoracic duct cannulated rat model at a dose level of 7 mg/kg. The rectal or intraperitoneal (i.p.) administration of CsA indicated a small amount of CsA in the plasma and in the lymph for 6 h. As oral routes, intrastomach (i.s.) and intraduodenal (i.d.) administration of CsA were performed and high lymph CsA levels were obtained. The i.s. administration of CsA resulted in the highest CsA levels in the lymph, 16 micrograms/ml, about twenty times higher than the rectal or i.p. administration. These results strongly support the usefulness of an oral CsA dosage form for the selective lymphatic delivery of CsA in clinical immunosuppressive therapy by means of a new mixed micelles system.