Graphene Oxide-Linezolid Combination as Potential New Anti-Tuberculosis Treatment

Abstract

Global pandemic management represents a serious issue for health systems. In some cases, repurposing of existing medications might help find compounds that have the unexpected potential to combat microorganisms. In the same way, changing cell–drug interaction by nanotechnology could represent an innovative strategy to fight infectious diseases. Tuberculosis (TB) remains one of the most alarming worldwide infectious diseases and there is an urgent need for new drugs and treatments, particularly for the emergence and spread of drug-resistant Mycobacterium tuberculosis (Mtb) strains. New nanotechnologies based on carbon nanomaterials are now being considered to improve anti-TB treatments, and graphene oxide (GO) showed interesting properties as an anti-TB drug. GO, which preferentially accumulates in the lungs and is degraded by macrophagic peroxidases, can trap Mycobacterium smegmatis and Mtb in a dose-dependent manner, reducing the entry of bacilli into macrophages. In this paper, combinations of isoniazid (INH), amikacin (AMK) and linezolid (LZD) and GO anti-mycobacterial properties were evaluated against Mtb H37Rv by using a checkerboard assay or an in vitro infection model. Different GO effects have been observed when incubated with INH, AMK or LZD. Whereas the INH and AMK anti-mycobacterial activities were blocked by GO co-administration, the LZD bactericidal effect increased in combination with GO. GO-LZD significantly reduced extracellular mycobacteria during infection and was able to kill internalized bacilli. GO-LZD co-administration is potentially a new promising anti-TB treatment at the forefront in fighting emerging antibiotic-resistant Mtb strains where LZD administration is suggested. This innovative pharmacological approach may lead to reduced treatment periods and decreased adverse effects. More importantly, we demonstrate how nanomaterials–drugs combinations can represent a possible strategy to quickly design drugs for pandemics treatment.

Penicillin and Oxacillin Loaded on PEGylated-Graphene Oxide to Enhance the Activity of the Antibiotics against Methicillin-Resistant Staphylococcus aureus

“…They also had used GO-PEG as a carrier for a specific antibiotic and confirmed the effectiveness of this carrier for improving the antibacterial activity of Tetracycline [ 62 ] (the same as the current study). Other studies have been conducted in this field that confirmed similar observations [ 66 , 67 , 68 ].…”

Nanoantibiotics: Functions and Properties at the Nanoscale to Combat Antibiotic Resistance

“…Graphene-oxide (GO) has a unique degree of in vivo specificity, biodegradability, low cellular toxicity, and enormous drug loading capacity ( McCallion et al, 2016 ). When administered in vivo , GO preferentially accumulates in lung cells ( De Maio et al, 2020 ) and inhibits the growth of Mycobacterium tuberculosis (Mtb), which is the prime microbial agent of tuberculosis infection ( Maio et al, 2019 ).…”

“…GO has been successfully coupled with Linezolid to treat Mycobacterium tuberculosis ( De Maio et al, 2020 ), also known as multi-drug-resistant TB or extensively drug-resistant TB (XDR-TB). Metronidazole could be combined with GO and biomimetic PLGA or membrane-bound NPs to treat Clostridiodes (clostridium) difficile infections.…”

Novel Structures and Applications of Graphene-Based Semiconductor Photocatalysts: Faceted Particles, Photonic Crystals, Antimicrobial and Magnetic Properties

“…Moreover, GO modification with organic compounds that possess the antimicrobial activity and biocompatibility have been intensively studied very recently, e.g., chitosan (CS) [92,[101][102][103], curcumin [104,105], antimicrobial agents (isoniazid (INH), amikacin (AMK) and linezolid (LZD), lincomycin hydrochloride (LMH), chloramphenicol (CPC) and gentamycin sulfate (GMS) [106,107]) and dyes [108]. Chitosan exhibits high biocompatibility, biodegradability and antibacterial properties [109].…”