Preclinical Studies of the Nebulized Delivery of Liposomal Amphotericin B

Abstract

Background: Intravenous liposomal amphotericin B (L-AMB) has accompanying side effects that may be diminished when administering an inhaled form. Delivery systems for inhaled or aerosolized L-AMB vary, and there has not been a recent comparison of available systems to date. Methods: We compared three differently designed nebulizer delivery systems for the inhaled delivery of L-AMB to determine the best combination of efficient lung dosing and treatment time. Aerosol size was measured using a Malvern Mastersizer, and five separate nebulizers were tested. For drug output measurements, a Harvard Lung was used, and aerosol was collected using HEPA filters. Results: Overall aerosol size characteristics were similar for all devices with volume median diameters in the 4-5 μm range. The highest inhaled dose was delivered by the AeroEclipse. The Aerogen and the AeroEclipse had similar predicted pulmonary doses, and the AeroEclipse had the highest pulmonary delivery rates. Conclusion: The AeroEclipse nebulizer may provide more efficient delivery in a shorter amount of time; however, human studies are warranted to assess the safety, tolerability, and efficacy of inhaled delivery of L-AMB from this system.

Keywords: aerosol; infectious disease; lung transplantation; pharmacology; pulmonology.