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Phenylethyl resorcinol (PR) is a potent tyrosinase inhibitor and a cosmeceutical skin lightening agent. However, the application of PR is limited by photoinstability and poor solubility. In this study, we formulated and optimized phenylethyl resorcinol loaded nanoliposomes (PR-NLPs) to improve the stability and effective delivery of PR. PR-NLPs were prepared by the ethanol injection method and optimized by a single factor experimental and Box–Behnken design. In addition, Diethylamino Hydroxybenzoyl Hexyl Benzoate (DHHB) as the UBA absorber was added to PR-NLPs, which significantly improved the photostability of PR. The mean size, polydispersity index (PDI), and zeta potential of the optimized PR-NLPs were 130.1 ± 3.54 nm, 0.225 ± 0.02, and −43.9 ± 3.44 mV, respectively. The drug encapsulation efficiency (EE) and loading efficiency (LC) of PR-NLPs were 96.81 ± 3.46% and 8.82 ± 0.6%, respectively. These PR-NLPs showed good physicochemical stability for 3 months at 4 °C and 25 °C in the dark. They showed typical sustained and prolonged drug-release behavior in vitro. The in vitro cytotoxicity assay and cellular uptake demonstrated that the PR-NLPs had excellent biocompatibility and cell transport ability. It significantly inhibited tyrosinase activity and reduced melanin production in B16F10 cells at concentrations of 20 or 30 μg/mL. Moreover, the PR-NLPs enhanced the PR into the skin. These results indicate that PR-NLPs can be used as a nanocarrier to improve the transdermal delivery of PR.

Nanoliposome Use to Improve the Stability of Phenylethyl Resorcinol and Serve as a Skin Penetration Enhancer for Skin Whitening