Vancomycin niosomal gel (Van-Nios Gel) enhances antibacterial, antibiofilm, and wound-healing activities against vancomycin-resistant Staphylococcus aureus (VRSA) in a diabetic wound model

The management of DFUs infected with drug-resistant bacteria, such as VRSA, remains a major clinical challenge. DFUs represent a significant therapeutic obstacle in clinical settings due to impaired healing and resistance to conventional antibiotics. This study investigates the potential of Van-Nios Gel to enhance antimicrobial efficacy and promote wound healing in a VRSA-infected DFU wound model. Van-Nios Gel was formulated with HPMC, a hydrophilic polymer, to improve drug retention and penetration at the infected site. The synthesized formulation was physicochemically characterized for hydrodynamic size, surface charge, and PDI by DLS, and its morphology was examined by SEM. Additionally, its EE% and in vitro drug release profile were evaluated. Furthermore, the in vitro antibacterial and antibiofilm activities were assessed by determining the MIC, MBC, biofilm inhibition (%), as well as the expression of biofilm‑related genes using RT‑qPCR. The hydrodynamic size and PDI of Van-Nios Gel to be 270.6 nm, and 0.665, respectively. In addition, our results showed that Van-Nios Gel had a three-dimensional porous structure with a high EE% (68.2). The antibacterial results showed that Van-Nios Gel decreased the MIC and MBC values of the free drug against VRSA isolate by 16-fold. In addition, Van‑Nios Gel significantly suppressed biofilm production ( P < 0.0001) and caused greater reductions in the expression of both biofilm‑related genes ( icaR and icaD ) compared with the free drug. The in vivo efficacy of the synthesized Van-Nios Gel was also evaluated in a full-thickness infected DFU wound model in Wistar rats. Van-Nios Gel demonstrated substantial healing efficacy compared to the free formulation, with reduced bacterial loads (CFU/g) and accelerated wound closure (%). In addition, histopathological analyses revealed that wounds treated with Van-Nios Gel showed significantly greater re-epithelialization, reduced inflammatory cell infiltration, and increased collagen deposition compared with the free formulation and control groups. These findings suggest that Van-Nios Gel enhances dermal drug delivery, improves therapeutic outcomes, and mitigates VRSA infection-related complications. The synthesized niosomal gel offers a promising alternative to conventional antibiotic therapy against drug-resistant skin infections, although further studies are needed to validate its clinical applicability. Overall, this study highlights the potential of niosomal gel as an advanced platform for topical antibiotic delivery to improve the management of VRSA-infected DFU wounds.