Development and Evaluation of Hydrogel-Thickened Nanoemulsion Containing Orientin, Isoorientin, Vitexin and Isovitexin as an Antioxidant Wound Dressing

The development of a water-in-oil-in-water nanoemulgel (NEG) containing orientin, isoorientin, vitexin, and isovitexin from oil palm ( Elaeis guineensis Jacq.) leaves (OPL-FCEE) was fabricated using a two-stage ultrasonication technique to enhance its antioxidant and wound healing properties. Hence, to design a stable double NEG system for topical administration, selections of appropriate components at optimized compositions were necessary. In the present study, some combinations of oils, lipophilic and hydrophilic emulsifiers, osmotic regulators, and gelling agents were investigated. Consequently, three NEGs (WOW1-3) were selected, and an in-depth physicochemical and biological evaluation was carried out. The final formulations appeared as white semisolid nanoemulgels with the desired spherical particle sizes (20–500 nm). Moreover, WOW2 showed improved physical, thermodynamic, and kinetic stability compared to WOW1 and WOW3. The NEGs were able to reach 72–90% encapsulation efficiency and 90–95% drug release. Additionally, the kinetic drug release of WOW2–3 fitted well with the Korsmeyer–Peppas model, whereas WOW1 followed the Higuchi model. In rheological studies, the NEGs exhibited shear thinning and pseudoplastic flow behaviors, while WOW1–2 demonstrated elastic properties. The FT-IR spectroscopy revealed the acceptable compatibility of OPL-FCEE with other nanoemulgel components. Furthermore, the encapsulation of OPL-FCEE in the formulation has enhanced the antioxidant and wound healing properties with no cytotoxic effect at low concentrations (< 500 g/mL). Therefore, with the fulfilment of the basic requirement for dermal semisolid formulation, the developed OPL-FCEE-NEGs could potentially be an effective yet strategic approach to promoting wound healing. Graphical Abstract