Sustained tissue drug concentrations following inhalation of liposome-encapsulated fentanyl in rabbits

Abstract

Liposomes are microscopic vesicles that can entrap drug molecules. Liposome-encapsulated fentanyl has been shown to provide sustained drug release following pulmonary administration. In this study, the effect of encapsulation efficiency (EE) of fentanyl within liposomes on the retention of fentanyl within the respiratory tract was examined. Liposomes with three different encapsulation efficiencies, 50% EE, 70% EE, and 90% EE, were manufactured with radiolabeled fentanyl and phospholipid dipalmitoyl phosphatidylcholine. The preparations were administered through an endotracheal tube to anesthetized rabbits, and the respiratory tracts were removed and analyzed for retention of fentanyl and DPPC at different time intervals. Increasing the encapsulation efficiency of fentanyl within liposomes is shown to prolong the retention of both fentanyl and DPPC within the respiratory tract. This suggests that the encapsulation efficiency can be manipulated to design a preparation to provide optimal therapeutic plasma fentanyl concentrations. The unencapsulated or “free” drug could act as a loading dose, and the slow, sustained release of fentanyl from the liposome depot in the lungs could act as a maintenance dose. Thus, this method of delivering a potent opioid, such as fentanyl, has the potential for clinical use in pain management.

Key Words :

• Fentanyl
• Liposome
• Opioid
• Pulmonary Administration
• Pulmonary Drug Delivery