In vitro investigation of inhalation delivery of nebulized liposomes

Ondrej Misik¹, Jana Szabova², Filip Mravec² & Frantisek Lizal¹

¹Faculty of Mechanical Engineering, Brno University of Technology, Technicka 2896/2, Brno, 616 69, Czech Republic

²Faculty of Chemistry, Brno University of Technology, Purkynova 464, Brno, 612 00, Czech Republic

Summary

Inhalation therapy is a promising way of drug delivery, but the suitable carrier system plays an important role in its effectiveness. The inhalation administration of two nebulized liposomal systems was investigated in this study. The first system contained dipalmitoylfosfatidylcholine (DPPC), polyethylene glycol (PEG) bonded to dipalmitoylphosphoethanolamine (DPPE), and cholesterol (Chol). The second one consisted of DPPC, phosphatidic acid (PA), and Chol. These systems were nebulized by 2 air-jet nebulizers (AJN): Pari LC Sprint, and Pari LC Sprint Star. The stability during nebulization was assessed for both systems and both nebulizers. Aerodynamic Particle Size Distribution (APSD) of nebulized aerosols was measured. According to the results of the stability and APSD (MMAD_{LC_Sprint_Star} 7.39 ± 0.24 µm; MMAD_{LC_Sprint} 9.79 ± 0.41 µm), the air-jet nebulizer PARI LC Sprint Star and DPPC-PA-Chol liposomal system were selected as the most promising choice among the tested cases. This combination was used for the investigation of the in vitro inhalation drug delivery. For this purpose, realistic replicas of upper airways and trachea were used and the liposomal vesicles were labeled with fluorescent dye to enable the local deposition evaluation. The nebulized system was inhaled into the airways model with a steady flow rate of 20 l/min and a realistic breathing pattern of a normal tidal breathing regime. In the case of inhalation at a fixed flow rate, more than 90 % of the aerosol mass penetrated below the trachea segment. In the case of the realistic breathing pattern, around 70 % of aerosol mass reached the region below the trachea.

Key Message

Inhalation of the liposomal system DPPC-PA-Chol nebulized by air-jet nebulizer Pari LC Sprint Star is a promising way for inhalation delivery of drugs with different physicochemical properties from the view of the liposomal stability as well as delivery below the upper airways.