Inhaled liposomal iloprost extend detectable plasma level and prolong reduction of hypoxia-induced pulmonary hypertension in rat

Background: The iloprost inhalation product, Ventavis®, has a short plasma half-life (5-25 mins) and requires frequent dosing (6-9 times per day) for treatment of pulmonary arterial hypertension. Aim: Liposome formulation is employed to provide sustained plasma concentration, which is also expected to prolong pharmacological effect. Methods: The liposomal iloprost solution was prepared and characterized in terms of assay and encapsulation efficiency. The test articles were administered by microsprayer for pharmacokinetic (PK) study in rats and pharmacodynamic (PD) study in hypoxia-induced PH rats. Blood samples over 12 hours post-dosing were taken and analyzed by LC-MS-MS. Pulmonary arterial pressure was recorded by implanted probe through the hypoxia experiment. Results: Liposomal iloprost solution extended a detectable plasma level up to 8 hours in rats, as compared to iloprost solution which disappeared in one hour. High drug encapsulation reduces a dumping phenomena caused by iloprost solution. In hypoxia-induced rat model the pulmonary arterial pressures were reduced and returned to baseline immediately by iloprost solution. However, the reduction was significantly prolonged by liposomal iloprost. Conclusion: A stable liposomal iloprost solution demonstrates an extended plasma level and sustained pharmacological effects.