Fighting microbes the ‘Nano’ way

Sir,

Having read with great interest the article ‘Introduction to metallic nanoparticles’[1] by Mody et al., I wanted to focus on how nanotechnology has the potential to influence antibiotic/antifungal properties.

Improved dissemination of drugs and heightened efficacy, the current need of the hour, are now possible with the use of nanotechnology which increases the bioavailability and concentration at infection sites without significant toxicity and helps reduce the amount of drug required, the number of doses and bioinactivation.

A study found that an emulsion preparation of polyacrylate nanoparticles in which an N-thiolated β-lactam antibiotic is covalently conjugated onto the polymer framework had potent in vitro antibacterial properties against Methicillin-Resistant Staphylococcus Aureus (MRSA) and stability toward β-lactamase.[2] This technique enables us to modulate the antibiotic properties (like release profiles) of the nanoparticles by altering the length or location of the acrylate linker on the drug monomer and post-synthetic modification can be bypassed. A study testing the antimicrobial activity of levofloxacin-loaded polymeric nanoparticles on Escherichia coli (E. coli) biofilm cells concluded that antibiotic release profiles (initial high exposure better than slower release at the same dose) are as important as the dosage.

Nanoparticle release of nitric oxide has shown to considerably curb the MRSA infection and accelerate infected wound closure (with decreased suppurative inflammation, minimal bacterial burden, and less collagen degradation). Another study evaluated the efficacy of ciprofloxacin-encapsulated poly DL-lactide-co-glycolide copolymer nanoparticles on E. coli and concluded that the nano form of ciprofloxacin is superior to the free form in vivo.[3]

Silver has been shown to be a promising antimicrobial agent with considerably less toxicity. An antimicrobial gel formulation (ensuring sustained release) containing silver nanoparticles (7–20 nm) showed good antimicrobial (more effective on Gram-negative than Gram-positive bacteria) and antifungal activity and was found to be synergistic with ceftazidime and additive with streptomycin, kanamycin, ampiclox and polymyxin B.[4] Silver showed highest enhancement of antibacterial activity in combination with vancomycin, amoxicillin, and penicillin G against Staphylococcus aureus. It also demonstrated decent anti-inflammatory properties (as shown by concentration-dependent inhibition of marker enzymes-matrix metalloproteinase 2 and 9). Although shown to elicit an oxidative stress, cellular antioxidant systems (reduced glutathione content, superoxide dismutase, catalase) get triggered and prevent oxidative damage. Topical preparations proved completely safe and demonstrated scarless healing. Silver Carbene Complex-10 loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) was found to exhibit excellent antimicrobial activity in vitro and in vivo against Pseudomonas aeruginosa. Cefaclor-reduced gold nanoparticles demonstrate potent antimicrobial activity against both Gram-positive and Gram-negative bacteria as compared to cefaclor or gold nanoparticles alone. The mechanism behind such synergy is that while cefaclor inhibited the synthesis of the peptidoglycan layer, the gold nanoparticles generated “holes” in bacterial cell walls thereby increasing the permeability of the cell wall, leakage of cell contents and eventually cell death. Also, cationic nanoparticles (formed by cholesterol-conjugated G₃R₆TAT) show antifungal efficacy comparable to amphotericin-B against Cryptococcus neoformans.

Nanotechnology certainly boosts our fight against microbial infections and there is an obvious need for its far-reaching use.