Antifungal activity of oral (Tragacanth/acrylic acid) Amphotericin B carrier for systemic candidiasis: in vitro and in vivo study
- 243 Downloads
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.
KeywordsRadiation polymerization Tragacanth Site-specific drug carrier Amphotericin B Systemic candidiasis Antifungal activity
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Diro E, van Griensven J, Mohammed R, Colebunders R, Asefa M, Hailu A, et al. Atypical manifestations of visceral leishmaniasis in patients with HIV in north Ethiopia: a gap in guidelines for the management of opportunistic infections in resource poor settings. Lancet Infect Dis. 2015;15(1):122–9. https://doi.org/10.1016/s1473-3099(14)70833-3.CrossRefPubMedGoogle Scholar
- 8.Ostroha J, Pong M, Lowman A, Dan N. Controlling the collapse/swelling transition in charged hydrogels. Biomaterials. 2004;25(18):4345–53. https://doi.org/10.1016/j.biomaterials.2003.11.019.CrossRefPubMedGoogle Scholar
- 11.Ranjbar-Mohammadi M, Rabbani S, Bahrami SH, Joghataei MT, Moayer F. Antibacterial performance and in vivo diabetic wound healing of curcumin loaded gum tragacanth/poly(ε-caprolactone) electrospun nanofibers. Mater Sci Eng C. 2016;69:1183–91. https://doi.org/10.1016/j.msec.2016.08.032.CrossRefGoogle Scholar
- 14.Zohuriaan MJ, Shokrolahi F. Thermal studies on natural and modified gums. Polym Test. 2004;23(5):575–9. https://doi.org/10.1016/j.polymertesting.2003.11.001.CrossRefGoogle Scholar
- 23.Maggi L, Segale L, Ochoa Machiste E, Faucitano A, Buttafava A, Conte U. Polymers-gamma ray interaction. Effects of gamma irradiation on modified release drug delivery systems for oral administration. Int J Pharm. 2004;269(2):343–51. https://doi.org/10.1016/j.ijpharm.2003.09.027.CrossRefPubMedGoogle Scholar
- 24.Chapiro A. Radiation chemistry of polymers, basic mechanisms in the radiation chemistry of aqueous media. Radiat Res Suppl. 1964;4:451–55. https://doi.org/10.2307/3583578.
- 28.Montgomery H, Dymock JF. Determination of nitrite in water. Analyst. 1961;86(102):414-&.Google Scholar
- 36.Ibrahim F, Gershkovich P, Sivak O, Wasan EK, Bartlett K, Wasan KM. Efficacy and toxicity of a tropically stable lipid-based formulation of amphotericin B (iCo-010) in a rat model of invasive candidiasis. Int J Pharm. 2012;436(1–2):318–23. https://doi.org/10.1016/j.ijpharm.2012.06.062.CrossRefPubMedGoogle Scholar
- 40.Clancy CJ, Nguyen ML, Cheng SJ, Huang H, Fan GX, Jaber RA, et al. Immunoglobulin G responses to a panel of Candida albicans antigens as accurate and early markers for the presence of systemic candidiasis. J Clin Microbiol. 2008;46(5):1647–54. https://doi.org/10.1128/jcm.02018-07.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Ferrante A. Tumor necrosis factor alpha potentiates neutrophil antimicrobial activity—increased fungicidal activity against torulopsis-glabrata and candida-albicans and associated increases in oxygen radical production and lysosomal-enzyme release. Infect Immun. 1989;57(7):2115–22.PubMedPubMedCentralGoogle Scholar
- 48.Chin VK, Foong KJ, Maha A, Rusliza B, Norhafizah M, Chong PP. Multi-step pathogenesis and induction of local immune response by systemic Candida albicans infection in an intravenous challenge mouse model. Int J Mol Sci. 2014;15(8):14848–67. https://doi.org/10.3390/ijms150814848.CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Yamamoto Y, Klein TW, Friedman H. Involvement of mannose receptor in cytokine interleukin-1 beta (IL-1 beta), IL-6, and granulocyte-macrophage colony-stimulating factor responses, but not in chemokine macrophage inflammatory protein 1 beta (MIP-1 beta), MIP-2, and KC responses, caused by attachment of Candida albicans to macrophages. Infect Immun. 1997;65(3):1077–82.PubMedPubMedCentralGoogle Scholar
- 57.Adams ML, Kwon GS. Relative aggregation state and hemolytic activity of amphotericin B encapsulated by poly(ethylene oxide)-block-poly(N-hexyl-L-aspartamide)-acyl conjugate micelles: effects of acyl chain length. J Control Release. 2003;87(1–3):23–32. https://doi.org/10.1016/s0168-3659(02)00347-4.CrossRefPubMedGoogle Scholar