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Bioactivity, Safety, and Efficacy of Amphotericin B Nanomicellar Aerosols Using Sodium Deoxycholate Sulfate as the Lipid Carrier

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Abstract

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.

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Acknowledgements

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.

Funding

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).

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Authors and Affiliations

  1. Drug Delivery System Excellence Centre, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla, 90112, Thailand

    Faisal Usman, Titpawan Nakpheng & Teerapol Srichana

  2. 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

    Ruqaiya Khalil & Zaheer Ul-Haq

  3. Nanotec-PSU Excellence Centre on Drug Delivery System, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand

    Teerapol Srichana

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  1. Faisal Usman
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Correspondence to Teerapol Srichana.

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Usman, F., Khalil, R., Ul-Haq, Z. et al. Bioactivity, Safety, and Efficacy of Amphotericin B Nanomicellar Aerosols Using Sodium Deoxycholate Sulfate as the Lipid Carrier. AAPS PharmSciTech 19, 2077–2086 (2018). https://doi.org/10.1208/s12249-018-1013-4

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  • DOI: https://doi.org/10.1208/s12249-018-1013-4

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