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    Drug modifications: graphene oxide-chitosan loading enhanced anti-amoebic effects of pentamidine and doxycycline
    (SPRINGER, 28.11.2024) Jabri, Tooba; Daalah, Meshal; Alawfi, Bader S.; Gul, Jasra; Ahmed, Usman; Shah, Muhammad Raza; Khan, Naveed Ahmed; Siddiqui, Ruqaiyyah; Ying, Tan Yee; Tong, Yeo Jia; Anwar, Ayaz
    Acanthamoeba castellanii is the causative pathogen of a severe eye infection, known as Acanthamoeba keratitis and a life-threatening brain infection, named granulomatous amoebic encephalitis. Current treatments are problematic and costly and exhibit limited efficacy against Acanthamoeba parasite, especially the cyst stage. In parallel to drug discovery and drug repurposing efforts, drug modification is also an important approach to tackle infections, especially against neglected parasites such as free-living amoebae: Acanthamoeba. In this study, we determined whether modifying pentamidine and doxycycline through chitosan-functionalized graphene oxide loading enhances their anti-amoebic effects. Various concentrations of doxycycline, pentamidine, graphene oxide, chitosan-functionalized graphene oxide, and chitosan-functionalized graphene oxide loaded with doxycycline and pentamidine were investigated for amoebicidal effects against pathogenic A. castellanii belonging to the T4 genotype. Lactate dehydrogenase assays were performed to determine toxic effects of these various drugs and nanoconjugates against human cells. The findings revealed that chitosan-functionalized graphene oxide loaded with doxycycline demonstrated potent amoebicidal effects. Nanomaterials significantly (p < 0.05) inhibited excystation and encystation of A. castellanii without exhibiting toxic effects against human cells in a concentration-dependent manner, as compared with other formulations. These results indicate that drug modifications coupled with nanotechnology may be a viable avenue in the rationale development of effective therapies against Acanthamoeba infections.
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    Drug modifications: graphene oxide-chitosan loading enhanced anti-amoebic effects of pentamidine and doxycycline
    (Springer Science and Business Media Deutschland GmbH, 2024) Jabri, Tooba; Daalah, Meshal; Alawfi, Bader S.; Gul, Jasra; Ahmed, Usman; Shah, Muhammad Raza; Khan, Naveed Ahmed; Siddiqui, Ruqaiyyah; Ying, Tan Yee; Tong, Yeo Jia; Anwar, Ayaz
    Acanthamoeba castellanii is the causative pathogen of a severe eye infection, known as Acanthamoeba keratitis and a life-threatening brain infection, named granulomatous amoebic encephalitis. Current treatments are problematic and costly and exhibit limited efficacy against Acanthamoeba parasite, especially the cyst stage. In parallel to drug discovery and drug repurposing efforts, drug modification is also an important approach to tackle infections, especially against neglected parasites such as free-living amoebae: Acanthamoeba. In this study, we determined whether modifying pentamidine and doxycycline through chitosan-functionalized graphene oxide loading enhances their anti-amoebic effects. Various concentrations of doxycycline, pentamidine, graphene oxide, chitosan-functionalized graphene oxide, and chitosan-functionalized graphene oxide loaded with doxycycline and pentamidine were investigated for amoebicidal effects against pathogenic A. castellanii belonging to the T4 genotype. Lactate dehydrogenase assays were performed to determine toxic effects of these various drugs and nanoconjugates against human cells. The findings revealed that chitosan-functionalized graphene oxide loaded with doxycycline demonstrated potent amoebicidal effects. Nanomaterials significantly (p < 0.05) inhibited excystation and encystation of A. castellanii without exhibiting toxic effects against human cells in a concentration-dependent manner, as compared with other formulations. These results indicate that drug modifications coupled with nanotechnology may be a viable avenue in the rationale development of effective therapies against Acanthamoeba infections. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.