Inhaled liposomal iloprost shows high drug encapsulation, extended release profile and potentials of improving patient compliance

Background: Iloprost is a prostacyclin (PGI₂) analog for treatment of pulmonary arterial hypertension. The iloprost inhalation product, Ventavis®, has a short plasma half-life and requires frequent dosing (6-9 times per day). Moreover, iloprost therapy is associated with a number of side effects. AIM: To reduce dosing frequency, alleviate side effects, and provide sustained plasma concentration, Pharmosa Biopharm Inc (PBI) developed a liposomal iloprost formulation through oral inhalation. Methods: A series of liposomal iloprost formulations were prepared and characterized in terms of encapsulation efficiency and in-vitro release. The extended release formulations were selected for preclinical pharmacokinetic (PK) study through pulmonary delivery by microsprayer. Blood samples over 12 hours post-dosing were taken and analyzed by LC-MS-MS. Results: Liposomal iloprost solution is comprised of sub-micron sized liposomes which are stable sufficiently for practical daily use. Also, liposomes maintained stable in terms of encapsulation and hydrodynamic particle size after nebulization. The formulations achieved a high concentration with encapsulation efficiency greater than 90%. In-vitro release test in simulated lung fluid (SLF) indicated no-burst and sustained release. In PK study, plasma peak (Cmax) is several-fold lower than the iloprost solution. Conclusion: A stable liposomal iloprost solution demonstrates a sustained-release profile and no burst release in-vitro and in-vivo. It is expected to extend therapeutic effect as well as mitigate drug-related side-effects with fewer inhalations per day, then improving quality of life and patient compliance.