Gold Nanoparticle-Based Resuscitation of Cefoxitin against Clinical Pathogens: A Nano-Antibiotic Strategy to Overcome Resistance

Abstract

Gold nanoparticles have gained popularity as an effective drug delivery vehicle due to their unique features. In fact, antibiotics transported via gold nanoparticles have significantly enhanced their potency in the recent past. The present study used an approach to synthesize gold nanoparticles in one step with the help of cefoxitin antibiotic as a reducing and stabilizing agent. Cefoxitin is a second-generation cephalosporin that loses its potential due to modification in the porins (ompK35 and ompK36) of Gram-negative pathogens. Thus, the present study has developed an idea to revive the potential of cefoxitin against clinical Gram-negative pathogens, i.e., Escherichia coli and Klebsiella pneumoniae, via applying gold nanoparticles as a delivery tool. Prior to antibacterial activity, characterization of cefoxitin–gold nanoparticles was performed via UV–visible spectrophotometry, dynamic light scattering, and electron microscopy. A characteristic UV–visible scan peak for gold nanoparticles was observed at 518 nm, ζ potential was estimated as −23.6 ± 1.6, and TEM estimated the size in the range of 2–12 nm. Moreover, cefoxitin loading efficiency on gold nanoparticles was calculated to be 71.92%. The antibacterial assay revealed that cefoxitin, after loading onto the gold nanoparticles, become potent against cefoxitin-resistant E. coli and K. pneumoniae, and their MIC50 values were estimated as 1.5 μg/mL and 2.5 μg/mL, respectively. Here, gold nanoparticles effectively deliver cefoxitin to the resistant pathogens, and convert it from unresponsive to a potent antibiotic. However, to obtain some convincing conclusions on the human relevance, their fate and toxicity need to be evaluated.

Nano-Conversion of Ineffective Cephalosporins into Potent One against Resistant Clinical Uro-Pathogens via Gold Nanoparticles

“…Moreover, loading/attachment of desired drug onto AuNPs is itself a tedious job that might include the use of harsh chemicals such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide [ 19 , 46 ]. Hence, researchers developed one pot-AuNPs synthesis approach where the drug itself acts as a reducing and stabilizing agent to lessen the use of chemicals and ease the process of drug loading [ 11 , 12 , 13 , 14 , 15 , 24 ]. A similar approach was applied in the current study to synthesize AuNPs by two different generations of cephalosporins [2nd generation-Cefotetan (CT) and 3rd generation-Cefixime (CX)].…”

“…Second-generation (CT) and third-generation (CX) cephalosporin antibiotics at 250 μg concentration were added to a 3 mL reaction mixture containing 1 mM gold chloride salt (prepared in 7.2 pH phosphate buffer), separately [ 11 ]. Further, both the reaction mixtures were incubated at 40 °C for two days.…”

“…Thus, the current grave situation demands better alternative therapeutic options. Interestingly, nanoparticles could deliver antibiotics effectively to the resistant pathogen, and aid in converting unresponsive antibiotics into potent ones [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. In fact, a large surface area: volume ratio of nanoparticles enables a number of antibiotic molecules to attach to it and prepare a multivalent nano-antibiotic against the resistant pathogen [ 20 ].…”

“…In fact, AuNPs have helped to form successful nano-antibiotics by effectively grafting antibiotic molecules on their surface without compromising or damaging the active moiety of the attached antibiotic [ 19 , 20 , 24 , 25 ]. Moreover, the synthesis of AuNPs-based nano-antibiotics does not require a complex technique, a simple one-pot synthesis approach where the antibiotic itself acts as a reducing and capping agent could be adequate [ 11 , 12 , 13 , 14 , 15 , 24 ]. In the present study, AuNPs were explored as a delivery tool for two different generations of cephalosporin antibiotics i.e., 2nd generation- cefotetan (CT) and 3rd generation-cefixime (CX).…”

Synthesis and Study of Palladium Mono- and Bimetallic (with Ag and Pt) Nanoparticles in Catalytic and Membrane Hydrogen Processes

“…Nowadays, the nanotechnology field has significantly strengthened its position in many branches of human activity [ 1 , 2 , 3 , 4 , 5 , 6 ]. The design, development, and study of nanostructures attract the great attention of scientists all around the world because of the wide range of nanoparticle applications.…”