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Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation

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Abstract

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05–0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.

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Acknowledgements

This research work was supported by Sunway University, Malaysia, and University of Karachi, Pakistan.

Funding

This work was supported by Sunway University, Malaysia GRTIN-RRO-46–2022. Ruqaiyyah Siddiqui and Naveed Ahmed Khan are supported by the Air Force Office of Scientific Research (AFOSR), USA, (FA9550-23–1-0711).

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Authors and Affiliations

  1. International Center for Chemical and Biological Sciences, HEJ Research Institute of Chemistry, Karachi University, Karachi, 75270, Pakistan

    Komal Rao, Muhammad Abdullah & Muhammad Raza Shah

  2. Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, 47500, Subang Jaya, Selangor, Malaysia

    Usman Ahmed, Hashi Isse Wehelie & Ayaz Anwar

  3. Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University Edinburgh, Edinburgh, EH14 4AS, UK

    Ruqaiyyah Siddiqui

  4. Microbiota Research Center, Istinye University, 34010, Istanbul, Turkey

    Ruqaiyyah Siddiqui & Naveed A. Khan

  5. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, 42353, Madinah, Saudi Arabia

    Bader S. Alawfi

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  1. Komal Rao
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Contributions

AA, MA, MRA and NAK conceptualized the study. KR, MA, AA, UA carried out all experimental work under the supervision of MRA, HIW, BSA, RS and NAK. KR, AA, UA, MRA prepared the first draft of the manuscript, and MA, HIW, BSA, RS and NAK revised and corrected the manuscript. All authors approved the final manuscript.

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Correspondence to Naveed A. Khan or Ayaz Anwar.

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Rao, K., Abdullah, M., Ahmed, U. et al. Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation. Arch Microbiol 206, 134 (2024). https://doi.org/10.1007/s00203-024-03854-3

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