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

Rao, Komal and Abdullah, Muhammad and Usman, Ahmed * and Hashi, Isse Wehelie * and Shah, Muhammad Raza and Siddiqui, Ruqiayyah and Khan, Naveed A and Alawfi, Bader S and Ayaz, Anwar * (2024) Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation. Archives of Microbiology, 206 (134). ISSN 1432-072X

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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.

Item Type: Article
Uncontrolled Keywords: Acanthamoeba; central nervous system; free-living amoebae; infectious diseases; itraconazole; micelles; nanoformulation; nanotechnology;
Subjects: Q Science > QD Chemistry
Q Science > QL Zoology
Divisions: Others > Non Sunway Academics
Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Dept. Biological Sciences
Depositing User: Ms Yong Yee Chan
Related URLs:
Date Deposited: 13 May 2024 00:03
Last Modified: 13 May 2024 00:03
URI: http://eprints.sunway.edu.my/id/eprint/2580

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