<![CDATA[Resveratrol is a potent polyphenolic antioxidant with poor aqueous solubility and light sensitivity, which limit its topical application. This study developed and optimized a resveratrol self-nanoemulsifying drug delivery system (SNEDDS), incorporated the optimized system into a gel, and compared its physical characteristics, antioxidant activity, and in vitro release with those of a conventional resveratrol gel. A 16-run D-optimal mixture design was employed using virgin coconut oil (10–20%), Tween 80 (50–80%), and polyethylene glycol 400 (10–30%) as the oil, surfactant, and co-surfactant. The optimized composition consisted of 13.8131% virgin coconut oil, 61.7834% Tween 80, and 24.4036% polyethylene glycol 400, with a desirability value of 0.829. Experimental verification yielded a droplet size of 15.23 nm, emulsification time of 8.12 s, transmittance of 99.63%, drug loading of 46.51 mg/mL, polydispersity index of 0.157, and zeta potential of −11.77 mV, with no significant differences from the predicted values (p>0.05). The optimized SNEDDS gel exhibited good homogeneity and physical stability. DPPH radical-scavenging activity was stronger for the SNEDDS gel than for the conventional resveratrol gel, with IC₅₀ values of 7.25±0.02 and 9.01±0.03 µg/mL and antioxidant activity indices of 5.45±0.012 and 4.38±0.013, respectively. At 120 min, cumulative resveratrol release reached 155.28 µg/cm² (62.11%) for the SNEDDS gel compared with 134.35 µg/cm² (53.74%) for the conventional gel, representing a 15.6% higher release (p=0.046). Overall, the optimized SNEDDS gel enhanced antioxidant activity and in vitro release, demonstrating potential for improved topical resveratrol delivery.]]>
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