The emergence of multidrug resistant strains of Pseudomonas aeruginosa necessitates the exploration of novel therapeutic intervention (s). The present study aimed to develop a
nisin loaded
carbopol gel formulation (NLCG) and explore its therapeutic efficacy against P. aeruginosa infected
burn wounds. The formulation was prepared using
Carbopol 940 as a
polymer and characterized in terms of its appearance, stability, pH, rheology, spreadability, release, and permeation profiles. Disc diffusion assay and field emission scanning electron microscopy were carried out to establish in vitro antibacterial activity while the in vitro cytotoxicity was evaluated by hemolytic and
trypan blue exclusion assay. Furthermore, in vivo efficacy was investigated by developing P. aeruginosa infected third-degree murine
burn wound model followed by evaluation of parameters like bacterial loads, skin restoration, histopathological architecture, levels of
hydroxyproline,
myeloperoxidase and
cytokines. Our studies yielded a stable formulation with pH, viscosity and drug release flux values
as 6.5 ± 0.02, 382.4 p and 160.55 ± 3.64 μg h-1 cm-2 , respectively. Approximately, 84.02 ± 1.63% of
nisin was found to permeate into murine skin, further, affirmed by confocal microscopic observations. Interestingly, no in vitro cytotoxicity of NLCG (to erythrocytes and/or to peritoneal macrophages) could be observed. The log units decrease (s) in CFUs of Pseudomonas in skin were found to be 1.5137, 4.2257, 6.456 after 12, 24 and 72 h of topical gel
therapy, respectively. Percentage
wound closure, tensile strength, histological, and scanning electron microscopic studies further provided a healing evidence with skin showing restoration of the epithelium. The gel
therapy also led to a significant modulation (p ≤ 0.05) in
hydroxyproline content,
myeloperoxidase levels, and serum levels of
IL-1,
IL-10, and TNF-α. Our formulation revealed anti-Pseudomonas, wound healing, and immunomodulatory efficacy of NLCG. Further investigations are warranted to determine the underlying mechanism (s) of these displayed antibacterial and immunomodulatory effects.