Title : Neutral pH plasma-activated water as a surface disinfectant and wound healing solution to reduce the spread of nosocomial infections
Abstract:
Plasma activated water (PAW) is generated by introduction of air plasma over the surface of water under a specific voltage leading to the generation of numerous short-lived and long-lived reactive species precisely ROS (reactive oxygen species) and RNS (reactive nitrogen species). It holds widespread applications across the food, agricultural, and healthcare sectors. Previous literature indicates that the antimicrobial efficacy of PAW is predominantly attributed to its acidic pH. To enhance clinical and practical utility, our group formulated hs-PAbW, a neutral-pH PAW, and investigated its antimicrobial activity and mechanism of action against ESKAPE pathogens, which are frequently linked to hospital-acquired infections, particularly surgical site infections. Characterization of the reactive species confirmed that this formulation achieved the highest concentrations of ROS and RNS reported to date (H2O2+NO2- : 865±80 mg/l) while maintaining the neutral pH. hs-PAbW substantially lowered the bacterial burden of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii in their exponential phase upon a short exposure of 45 minutes. This bactericidal action was driven primarily by reactive nitrogen species, specifically the short-lived peroxy-nitrite species through nitro-tyrosine formation rather than reactive oxygen species alone.
A hydrogel containing hs-PAbW was developed at a bactericidal and non-cytotoxic dose (20% of hs-PAbW, termed as hs-PAbW-20), and its efficacy was tested in different murine wound infection models. When applied to the wounds of BALB/c mice, hs-PAbW-20 gel markedly lowered the burden of Pseudomonas aeruginosa and Staphylococcus aureus, which is comparable to the efficacy of commercially available ointments neosporin and soframycin. Furthermore, the gel fastened wound closure through the modulation of genes crucial for wound repair. In a diabetic C57BL/6 mouse model, hs-PAbW-20 gel similarly reduced the P. aeruginosa burden and helped in faster healing. Collectively, these results demonstrate that hs-PAbW-20 gel serves as a promising next-generation alternative to antibiotic-based wound therapies.
