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Antifungal activity of oral (Tragacanth/acrylic acid) Amphotericin B carrier for systemic candidiasis: in vitro and in vivo study

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Abstract

In an effort to increase the oral bioavailability of Amphotericin B (AmB), a pH-sensitive drug carrier composed of Tragacanth (Trag) and acrylic acid (AAc) was prepared using γ-irradiation. The swelling behavior of (Trag/AAc) hydrogels was characterized as a function of pH and ionic strength of the swelling medium. The obtained swelling indices revealed the ability of the prepared hydrogel to protect a loaded drug in stomach-simulated medium (Fickian behavior) and to release such drug in intestinal-simulated medium (non-Fickian behavior). In vitro release studies of the antifungal (AmB) were performed to evaluate the hydrogel potential as a drug carrier. The antifungal activity of the prepared oral formulation was investigated in a mouse model of systemic candidiasis. Data revealed that (Trag/AAc)-AmB has a potent antifungal efficacy as demonstrated by prolonging the survival time and reducing the tissue fungal burden, serum antibody titers, as well as inflammatory cytokines in kidney and liver tissues. Furthermore, in vivo toxicity of (Trag/AAc)-AmB was assessed via measuring kidney and liver functions, and results displayed the safety of this novel AmB formulation which was confirmed by histopathological examination. Overall, results indicated that the prepared (Trag/AAc)-AmB is an effective oral delivery system for AmB with better bioavailability and minimal toxicity and could represent a promising approach for improving the therapeutic index of the drug.

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Acknowledgements

The authors are very grateful to Prof. Dr. Kawkab A. Ahmed (Pathology Department, Faculty of Veterinary Medicine, Cairo University, Egypt) for her assistance in examining and interpreting histopathologic aspects this work.

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Authors and Affiliations

  1. Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Atomic Energy Authority, P.O. Box 29, Nasr City, Cairo, Egypt

    Heba A. Mohamed & Rasha R. Radwan

  2. Polymer Chemistry Department, National Center for Radiation Research and Technology (NCRRT), Atomic Energy Authority, P.O. Box 29, Nasr City, Cairo, Egypt

    Amany I. Raafat & Amr El-Hag Ali

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  1. Heba A. Mohamed
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Mohamed, H.A., Radwan, R.R., Raafat, A.I. et al. Antifungal activity of oral (Tragacanth/acrylic acid) Amphotericin B carrier for systemic candidiasis: in vitro and in vivo study. Drug Deliv. and Transl. Res. 8, 191–203 (2018). https://doi.org/10.1007/s13346-017-0452-x

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