Co-encapsulated xanthoxylin (GX-50) and vitamin C (Vc) microcapsules (GX-50-Vc-M) were prepared by the combination of a water-in-oil-in-water (W1/O/W2) double emulsion with complex coacervation. The W1/O/W2 double emulsion was prepared by two-step emulsification, and it has a uniform particle size of 8.388 μm and high encapsulation efficiencies of GX-50 (85.95%) and Vc (67.35%) under optimized process conditions. Complex coacervation occurs at pHs 4.0-4.7, which has the highest encapsulation efficiency of GX-50 and Vc at pH 4.5. The complex coacervate with tannic acid solidifying (namely, wet microcapsules) has better mechanical properties and also enhances the ability of co-encapsulation of active ingredients. The resulting microcapsules by freeze-drying of wet microcapsules were characterized by UV-vis absorbance spectroscopy (UV-vis), Fourier infrared spectroscopy (FI-IR), confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), X-ray diffraction (XRD), 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical scavenging, and in vitro permeation measurements. Under optimal conditions, the encapsulation efficiency and drug loading of GX-50-Vc-M for GX-50 and Vc are, respectively, 78.38 ± 0.51 and 59.34 ± 0.56%, and 35.6 ± 0.68 and 29.8 ± 0.92%. A slight shift in the FTIR peak between single GX-50 or Vc and GX-50-Vc-M confirmed the successful co-encapsulation of GX-50 and Vc in microcapsules. GX-50-Vc-M has bridged irregular spherical aggregates, while GX-50 and Vc are, respectively, encapsulated in hydrophobic and hydrophilic cavities of microcapsules in an amorphous dissolved state. GX-50-Vc-M has the highest DPPH· radical scavenging rate of 62.51%, and the scavenging process of GX-50-Vc-M on DPPH· radicals is more in line with the pseudo-second-order kinetic equation model. Moreover, the in vitro permeation of GX-50 and Vc in GX-50-Vc-M can reach maximum values of 40 and 60%, respectively. This concludes that GX-50-Vc-M is a promising delivery system for the penetration of the antioxidant into the deeper layers of the skin for the antioxidant effect.
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