Products Cited in Publications Worldwide Drug modifications: graphene oxide-chitosan loading enhanced anti-amoebic effects of pentamidine and doxycycline

Drug modifications: graphene oxide-chitosan loading enhanced anti-amoebic effects of pentamidine and doxycycline

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

DOI: PMID:

Abstract

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 efcacy against Acanthamoeba parasite, especially the cyst stage. In parallel to drug discovery and drug repurposing eforts, drug modifcation 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 efects. 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 efects against pathogenic A. castellanii belonging to the T4 genotype. Lactate dehydrogenase assays were performed to determine toxic efects of these various drugs and nanoconjugates against human cells. The fndings revealed that chitosan-functionalized graphene oxide loaded with doxycycline demonstrated potent amoebicidal efects. Nanomaterials signifcantly (p<0.05) inhibited excystation and encystation of A. castellanii without exhibiting toxic efects against human cells in a concentration-dependent manner, as compared with other formulations. These results indicate that drug modifcations coupled with nanotechnology may be a viable avenue in the rationale development of efective therapies against Acanthamoeba infections.

Keywords

Drug modifcation ; Graphene oxide ; Chitosan ; Doxycycline ; Pentamidine ; Acanthamoeba

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