Tracking success of interaction of green-synthesized Carbopol nanoemulgel (neomycin-decorated Ag/ZnO nanocomposite) with wound-based MDR bacteria

Abstract Multidrug-resistant wound infections are a global health threat and a leading cause of death, persisting despite available treatments due to antibiotic resistance, biofilms, and ineffective drug delivery systems. The aim of this study is to (i) formulate an innovative nano-drug delivery system (NDDS) based on a Carbopol nanoemulgel (NEG) co-loaded with neomycin-silver/zinc oxide nanocomposite (NC) that could fight clinical MDR and treat biofilm-forming wound pathogens through topical application, and (ii) assess its in vivo wound-healing potential. The silver/zinc oxide (Ag/ZnO) NC was synthesized by co-inoculating the metabolites of Aspergillus welwitschiae and Meyerozyma guilliermondii . The synthesized NC was then conjugated with neomycin and loaded into a Carbopol NEG for efficient topical delivery. The resulting Neo-Ag/ZnO NEG was characterized physicochemically ( e.g. , UV-visible [UV-Vis] spectrophotometry, field emission scanning electron microscopy, X-ray diffraction, and Fourier transform infrared [FTIR] spectroscopy), biologically ( e.g. , in vitro antimicrobial, antibiofilm, and hemolytic activities), and pharmacologically ( e.g. , drug content, ex vivo drug release behavior, and in vivo wound-healing potential). The physicochemical analysis confirmed the successful mycosynthesis of the Carbopol NEG-loaded Neo-Ag/ZnO NC. SEM depicted a crystalline polyhedral shape of the small NC (average particle size of 38 nm). FTIR studies showed a slight interaction with the drug and other bioactive moieties in the Carbopol NEG. The Neo content in the Carbopol NEG was as high as 98%, and a maximum release of 81% for Neo, Ag, and ZnO ions was noticed after 12 h. The NDDS appeared hemocompatible and displayed a minimal inhibition concentration of 0.002 µg/mL with the greatest antimicrobial potential against S. aureus (an inhibition zone of 46 mm) compared to other tested wound microbes ( p < 0.05). Statistically significant wound-healing activity was found for NDDS ( p = 0.0001) in comparison to the control at a concentration of 100 mg/mL. The results showed that this newly developed Carbopol NEG-loaded neo-Ag/ZnO NC appeared promising for controlling resistant skin infections and boosting wound regeneration.