Bioactivity, Safety, and Efficacy of Amphotericin B Nanomicellar Aerosols Using Sodium Deoxycholate Sulfate as the Lipid Carrier
We report nanomicelles of amphotericin B (AmB) using various molar ratios of AmB and sodium deoxycholate sulfate (SDCS) for inhalation with improved stability, solubility, bioactivity, and safety. The particle sizes of all aerosolized formulations are expressed as mass median aerodynamic diameter (0.9–1.6 μm), fine particle fraction (70.3–86.5%), and geometric standard deviation (1.4–2.1) which indicated their sizes are appropriate for use as an inhaler. In vitro cytotoxicity studies conducted using respiratory and kidney cell lines demonstrated that the marketed Fungizone® was toxic to macrophage and embryonic kidney cells and cell viability decreased from 96 to 48% and from 97 to 67%, respectively when the AmB equivalent concentration was increased from 1 to 16 μg/mL. However, AmB-SDCS formulations showed no evidence of toxicity even up to 8 μg/mL compared to Fungizone®. Minimum inhibitory and fungicidal concentrations were significantly reduced against Cryptococcus neoformans, and Candida albicans. Also, antileishmanial activity significantly improved for AmB-SDCS formulations. There was an evidence of phagocytosis of the AmB-SDCS formulation by alveolar macrophages NR 8383. Molecular modeling studies suggested the role of hydrogen bonding in stabilization of the AmB-SDCS complex. This study indicated that AmB-SDCS nanomicelles can be used to design a safe and cost-effective AmB for inhalation.
KEY WORDSamphotericin B sodium deoxycholate sulfate toxicities phagocytosis molecular modeling
The authors also acknowledge the Computational Chemistry Unit, Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan, for the docking studies.
This research was funded by a grant from the 2014 scholarship awards for Masters and Ph.D. studies under Thailand’s Education Hub for Southern Region of ASEAN countries (TEH-AC).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict to declare.
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