Journal of Pharmacy Technology
29(5) 199–204
© The Author(s) 2013
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DOI: 10.1177/8755122513500905
pharmatech.sagepub.com
Article
Introduction
Invasive fungal infections of the lung are associated with
high mortality rates, with immunocompromised patients,
such as transplant recipients, being the most susceptible.
1,2
Amphotericin B, a polyene antifungal agent, remains an
important agent in the treatment against fungal infections.
3
Amphotericin B has high affinity for the ergosterol compo-
nent of fungal membranes, binds to it, and causes fungal
death.
4
The side effects of amphotericin B include renal tox-
icity, anemia, and hypokalemia. Encapsulation of ampho-
tericin B in liposomes or complexation with lipids (eg,
amphotericin B lipid complex [ABLC]; Abelcet, Sigma-Tau
Pharmaceuticals, Gaithersburg, MD) decreases its potential
toxicity. This occurs because encapsulation of amphotericin
B in liposomes promotes selective uptake of the drug by the
reticuloendothelial system and targeting of the ergosterol
component of the fungal membrane. As a result, the
500905PMT 29 5 10.1177/8755122513500905Journal of Pharmacy Technology Lambros et al
research-article 2013
1
Western University of Health Sciences, Pomona, CA, USA
2
University of Southern California, Los Angeles, CA, USA
Corresponding Author:
Maria Polikandritou Lambros, PhD, Department of Pharmaceutical
Sciences, Western University of Health Sciences, Pomona, CA 91766,
USA.
Email: mlambros@westernu.edu
Nebulizer Choice Affects the Airway
Targeting of Amphotericin B Lipid
Complex Aerosols
Maria Polikandritou Lambros, PhD
1
, Paul M. Beringer, PharmD
2
,
and Annie Wong-Beringer, PharmD, FIDSA
2
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.
Keywords
aerosols, liposomal aerosols, amphotericin B, nebulizers, lipid complex, liposomes