PULMONARY TARGETING OF LIPOSOMAL TRIAMCINOLONE ACETONIDE PHOSPHATE

Purpose. To explore the use of triamcinolone acetonide phosphate lipos omes as a pulmonary targeted drug delivery system. Methods. Triamcinol one acetonide phosphate liposomes composed of 1,2-distearoyl phosphati dylcholine and 1,2-distearoyl phosphatidyl glycerol and triamcinolone acetonide 21-phosphate dipotassium salt were prepared by dispersion an d extruded through polycarbonate membranes. Encapsulation efficiency a nd in vitro stability at 37 degrees C were assessed after size exclusi on chromatography. TAP liposomes (TAP-lip) or TAP in solution (TAP-sol ) were delivered to rats either by intratracheal instillation (IT) or intravenous (IV) administration. Pulmonary targeting was assessed by s imultaneous monitoring of glucocorticoid receptor occupancy over time in lung (local organ) and liver (systemic organ) using an ex vivo rece ptor binding assay as a pharmacodynamic measure of glucocorticoid acti on. Results. In vitro studies in different fluids over 24 hours, showe d that more than 75% of the TAP remained encapsulated in liposomes. Cu mulative pulmonary effects after IT administration of TAP-lip were 1.6 times higher than liver receptor occupancy. In contrast, there was no difference in the pulmonary and hepatic receptor occupancy time profi les when TAP was administered intratracheally as a solution. No prefer ential lung targeting was observed when TAP-lip was administered IV. A s indicated by the mean effect times, lung receptor occupancy was sust ained only when TAP-lip was administered IT. Conclusions. Intratrachea l administration of TAP-lip provided sustained receptor occupancy, and increased pulmonary targeting which was superior to IT administration of TAP-sol or IV administration of TAP-lip. The use of liposomes may represent a valuable approach to optimize sustained delivery of glucoc orticoids to the lungs via topical administration.