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

Komal Rao, Muhammad Abdullah, Usman Ahmed, Hashi Isse Wehelie, Muhammad Raza Shah, Ruqaiyyah Siddiqui, Naveed A. Khan*, Bader S. Alawfi, Ayaz Anwar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number134
JournalArchives of Microbiology
Volume206
Issue number4
Early online date4 Mar 2024
DOIs
Publication statusPublished - Apr 2024

Keywords

  • Acanthamoeba
  • Central nervous system
  • Free-living amoebae
  • Infectious diseases
  • Itraconazole
  • Micelles
  • Nanoformulation
  • Nanotechnology

ASJC Scopus subject areas

  • Microbiology
  • Biochemistry
  • Molecular Biology
  • Genetics

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