title: Aerosolized liposomal Amphotericin B: a potential prophylaxis of invasive pulmonary aspergillosis in immunocompromised patients.
abstract: BACKGROUND
  Aerosolized liposomal Amphotericin B may reduce the incidence of invasive pulmonary Aspergillosis in adults with chemotherapy-induced prolonged neutropenia with less nephrotoxicity. The breath-actuated AeroEclipse® BAN nebulizer is very efficient and minimizes environmental drug contamination since no aerosol is produced, unless the patient is inspiring through the device. Our aim is to develop an appropriate delivery system suitable for children that does not disrupt the liposomes due to the shear forces in nebulization.
  
  
  METHODS
  This is an in vitro experimental study in vitro. Six ml of 4 mg/ml liposomal Amphotericin B solution (AmBisome®; Astellas Pharma Inc., Markham, Ontario, CA) was nebulized with the breath-actuated nebulizer (AeroEclipse®; Trudell Medical International, Canada) and captured by the glass liquid impinger. Sodium dodecyl sulfate was used as detergent to disrupt the liposomes in control samples. Gel filtration, electron microscopy, and high performance liquid chromatography (HPLC) were used to compare the size and shape of the liposomes, and amount of the drug before and after nebulization. The aerosol particle size was obtained by the laser diffraction.
  
  
  RESULTS
  After nebulization, 97.5% of amphotericin B was captured by the liquid impinger and detected by HPLC. Gel filtration and electron microscopy demonstrated that the drug remained in its liposomal configuration after nebulization. The mass median diameter (MMD) was 3.7 μm and 66% of aerosol particles were less than 5 μm in diameter.
  
  
  CONCLUSIONS
  We demonstrated that liposomal Amphotericin B can be nebulized successfully without disrupting the liposomes and minimize drug loss by using the breath-actuated nebulizer.
authors.affiliation: Division of Pulmonology, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Harutai
authors.initials: H
authors.lastname: Kamalaporn
authors.forename: Kitty
authors.initials: K
authors.lastname: Leung
authors.forename: Mark
authors.initials: M
authors.lastname: Nagel
authors.forename: Saranya
authors.initials: S
authors.lastname: Kittanakom
authors.forename: Battista
authors.initials: B
authors.lastname: Calvieri
authors.forename: Reinhart A F
authors.initials: RA
authors.lastname: Reithmeier
authors.forename: Allan L
authors.initials: AL
authors.lastname: Coates
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects*; D055744:Invasive Pulmonary Aspergillosis / Q000517:prevention & control*; D008854:Microscopy, Electron; D009330:Nebulizers and Vaporizers
chemical_list: D000336:Aerosols; D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B
keywords: AeroEclipse®; aerosolized liposomal amphotericin B; breath-actuated nebulizer; invasive pulmonary Aspergillosis