Nebulizer Choice Affects the Airway Targeting of Amphotericin B Lipid Complex Aerosols

Abstract

Background: Although amphotericin B is highly effective against fungal infections, it has serious adverse effects. Encapsulation of amphotericin B in liposomes reduces its potential for systemic side effects. Administration of liposomal amphotericin via aerosols to the lungs (a main portal of fungal infections) further reduces its toxicity while increasing its therapeutic index and prophylactic efficacy. However, the effectiveness of aerosol therapy depends on the dose deposited and the distribution of the drug within the lungs. The size of the aerosol particle is an important factor that affects the distribution of the drug within the lungs and the effectiveness of therapy. Objective: This study aims to determine the physicochemical suitability of amphotericin B lipid complex (ABLC) for aerosolization and to compare the performance of 3 commercially available air jet nebulizers in generating ABLC aerosols in terms of aerosol output (mg/min) and drug amount aerosolized within various particle-size ranges, the latter of which affects airway deposition. Methods: We aerosolized 2 concentrations (5 mg/mL and 10 mg/mL) of ABLC and evaluated their physicochemical properties, including osmolality, pH, and viscosity. The aerosolization performances of Pulmo-Aide/Micromist, Envoy/Sidestream, and Proneb/Pari LC Star systems were then evaluated in terms of output rate (mg/min), percent aerosolized, and milligram per minute of drug aerosolized within particle-size ranges of 1 to 3.5 µm, 3.5 to 6 µm, and 1 to 6 µm. Results: The output rate increased with higher drug concentration regardless of device. Pulmo-Aide/Micromist and Envoy/Sidestream showed high output rates. Proneb/Pari LC Star and Envoy/Sidestream delivered the highest percentages of aerosolized particles within the 1 to 3.5 µm particle-size range, favoring deposition within the alveolar/distal end area of the airways. Pulmo-Aide/Micromist delivered a higher percentage of aerosol within the 3.5 to 6 µm than the 1 to 3.5 µm particle-size range, favoring deposition in the central airways. Conclusion: The present study shows that different nebulizers produced different size ranges of aerosolized particles of ABLC preferentially targeting different parts of the airways. Thus, effective aerosol therapies may require the evaluation of different nebulizers for optimal targeting.