| Summary: | Cinnamaldehyde, the main phytoconstituent of the cinnamon oil, has been reported for its potential wound healing activity, associated to its antimicrobial and anti-inflammatory effects. In this study, we are reporting on the cinnamaldehyde-based self-nanoemulsifying drug delivery system (CA-SNEDDS), which was prepared and evaluated for its antimicrobial, antioxidant, anti-inflammatory, and wound healing potential using the rat third-degree skin injury model. The parameters, i.e., skin healing, proinflammatory, and oxidative/antioxidant markers, were evaluated after 3 weeks of treatment regimens with CA-SNEDDS. Twenty rats were divided randomly into negative control (untreated), SNEDDS control, silver sulfadiazine cream positive control (SS), and CA-SNEDDS groups. An aluminum cylinder (120 °C, 10-s duration) was used to induce 3rd-degree skin burns (1-inch square diameter each) on the rat’s dorsum. At the end of the experiment, skin biopsies were collected for biochemical analysis. The significantly reduced wound size in CA-SNEDDS compared to the negative group was observed. CA-SNEDDS-treated and SS-treated groups demonstrated significantly increased antioxidant biomarkers, i.e., superoxide dismutase (SOD) and catalase (CAT), and a significant reduction in the inflammatory marker, i.e., NAP-3, compared to the negative group. Compared to SNEDDS, CA-SNEDDS exhibited a substantial antimicrobial activity against all the tested organisms at the given dosage of 20 µL/disc. Among all the tested microorganisms, MRSA and <i>S. typhimurium</i> were the most susceptible bacteria, with an inhibition zone diameter (IZD) of 17.0 ± 0.3 mm and 19.0 ± 0.9 mm, respectively. CA-SNEDDS also exhibited strong antifungal activity against <i>C. albicans</i> and <i>A. niger</i>, with IZD of 35.0 ± 0.5 mm and 34.0 ± 0.5 mm, respectively. MIC and MBC of CA-SNEDDS for the tested bacteria ranged from 3.125 to 6.25 µL/mL and 6.25 to 12.5 µL/mL, respectively, while the MIC and MBC for <i>C. albicans</i> and <i>A. niger</i> were 1.56 µL/mL and 3.125 µL/mL, respectively. The MBIC and MBEC of CA-SNEDDS were also very significant for the tested bacteria and ranged from 6.25 to 12.5 µL/mL and 12.5 to 25.0 µL/mL, respectively, while the MBIC and MBEC for <i>C. albicans</i> and <i>A. niger</i> were 3.125 µL/mL and 6.25 µL/mL, respectively. Thus, the results indicated that CA-SNEDDS exhibited significant wound healing properties, which appeared to be attributed to the formulation’s antimicrobial, antioxidant, and anti-inflammatory effects.
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