To improve the retention time and skin-whitening efficacy of Atractylodes macrocephale essential oil (AMO), a novel Pickering emulsion based nanogel loaded with AMO (AMO-PEG) was successfully developed. This formulation employed nano-pearl powder (NPP) as the particle stabilizer for the Pickering emulsion and Bletilla striata polysaccharide (BSP) as the gel matrix. The pH, rheological properties, hardness, and elasticity of AMO-PEG were affected by the ratio of AMO-Pickering emulsion (AMO-PE) to BSP gel matrix. The results showed that AMO-PEG exhibited solid-like behavior and was capable of forming nanogels when the ratio of AMO-PE to BSP was 1:1. AMO-PE and AMO-PEG are two different dosage forms in the preparation of AMO. The effects of varying dosage forms on AMO were evaluated by in vitro transdermal release, skin irritation test, and skin-whitening effect. AMO-PEG conforms to the zero-order kinetic equation (R2 = 0.9189). The skin retention rate of AMO-PEG was 1.37 times higher than that of AMO-PE, indicating that AMO-PEG could continuously and slowly exert the whitening effect of the drugs. Compared with AMO-PE, AMO-PEG significantly increased the inhibition of tyrosinase activity and melanogenesis in B16F10 cells. AMO-PEG can promote the inhibition of B16F10 cells and improve the whitening effect of AMO and BSP. In conclusion, the Pickering emulsion based nanogel appears to be a promising strategy for enhancing the skin-whitening efficacy of both AMO and BSP.
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