A comparative dermatokinetic evaluation of thymoquinone-loaded nanoemulsion gel for enhanced wound healing and anti-inflammatory efficacy

Purpose: This study aims to design, formulate, and assess a Thymoquinone (TQN)-loaded nanoemulsion, which is further transformed into a nanoemulgel to enhance solubility, improve skin penetration with dermatokinetic properties, and optimize its topical application for wound healing and anti-inflammatory treatment. Since TQN has limited or poor water solubility, its therapeutic efficacy is directly impacted. Therefore, developing a TQN-NE gel is essential to enhance transdermal delivery. Methods: The TQN-loaded nanoemulsion (TQN-NE) was formulated using the aqueous microtitration method, incorporating Labrafil®M2125, i.e., oil, Tween 80, i.e., surfactant, and plurol oleique i.e., co-surfactant. To improve retention time for topical use, the nanoemulsion was combined with a carbopol 934-based gel, resulting in a nanoemulgel. Both nanoemulsion and nanoemulgel were analyzed by various parameters, including thermodynamic-stability, globule–size, physical–properties, pH, zeta potential, polydispersity index (PDI), drug content, rheological properties, permeation via skin, in vitro drug release, viscosity, -spreadability, shear stress, -bioadhesive strength, -swelling index, and adhesive force. Results: The TQN-NE6 formulation resulted in a transparent, stable, and well-defined nanoemulsion with an average droplet/globule size of 151.7 ± 5.93 nm, a ZP of − 18.10 ± 2.61 mV, and a polydispersity index of 0.197 ± 0.061. The Thymoquinone nanoemulsion gel (TQN-NE-Gel) exhibited a mean droplet size of 172.32 ± 6.94 nm, a PDI of 0.126 ± 0.123, a ZP of − 23.30 ± 0.45 mV, and a pH of 6.66 ± 0.08. It also demonstrated a viscosity of 5424 cP at 100 rpm and a spreadability factor of 0.129 ± 0.09 cm²/g, along with enhanced mucoadhesive strength and a smooth, spherical shape confirmed by TEM analysis. The optimized TQN-NE-Gel formulation significantly improved skin permeation, with dermatokinetic analysis showing a notable (p < 0.001) enhance in C_max and AUC_0–8 h in treated skin compared to conventional TQN gel. Additionally, the optimized TQN-NE-Gel demonstrated superior wound healing efficacy upon topical application. No signs of inflammatory cell infiltration were observed post-treatment, confirming the formulation’s safety and non-toxic nature. Conclusion: A novel TQN-NE-Gel was successfully developed, demonstrating enhanced solubility and improved skin permeation of Thymoquinone. The formulation exhibited superior efficacy in promoting wound healing and providing anti-inflammatory effects when applied topically. TQN-NE-Gel serves as an effective carrier for the Thymoquinone, facilitating improved transdermal delivery and therapeutic potential in future.