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Drug modifications: graphene oxide-chitosan loading enhanced anti-amoebic effects of pentamidine and doxycycline
Tooba Jabri1, Meshal Daalah2, Bader S Alawfi3
1International Center for Chemical and Biological Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi, 75270, Pakistan.
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 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.
Insights
Modified doxycycline loaded onto chitosan-functionalized graphene oxide shows potent anti-Acanthamoeba effects. This nanotechnology approach effectively inhibits parasite growth and cyst formation without harming human cells, offering a promising new therapy for Acanthamoeba infections.
Area of Science:
- Nanotechnology
- Infectious Diseases
- Parasitology
Background:
- Acanthamoeba castellanii causes severe keratitis and encephalitis.
- Current treatments for Acanthamoeba infections are limited, especially against the cyst stage.
- Drug modification and nanotechnology offer potential solutions for neglected parasitic infections.
Purpose of the Study:
- To investigate the enhanced anti-amoebic effects of pentamidine and doxycycline modified with chitosan-functionalized graphene oxide.
- To evaluate the efficacy of these nanoconjugates against pathogenic Acanthamoeba castellanii (T4 genotype).
- To assess the safety of these formulations on human cells.
Main Methods:
- Preparation and characterization of chitosan-functionalized graphene oxide loaded with doxycycline and pentamidine.
- Amoebicidal assays to determine efficacy against Acanthamoeba castellanii.
- Lactate dehydrogenase assays to evaluate cytotoxicity against human cells.
- Inhibition assays for excystation and encystation.
Main Results:
- Chitosan-functionalized graphene oxide loaded with doxycycline exhibited significant amoebicidal activity.
- The nanomaterial formulation effectively inhibited Acanthamoeba castellanii excystation and encystation (p < 0.05).
- The tested nanoconjugates showed no significant toxicity to human cells in a concentration-dependent manner.
Conclusions:
- Drug modification combined with nanotechnology presents a viable strategy for developing effective Acanthamoeba infection therapies.
- Chitosan-functionalized graphene oxide loaded with doxycycline is a promising candidate for treating Acanthamoeba infections.
- This approach offers a potential solution to overcome the limitations of current treatments, particularly against resistant parasite stages.
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