Galactosylation of Cosmetic Preservatives to Reduce Skin Permeation and Cytotoxicity

Cosmetic preservatives should have reduced percutaneous absorption to lower the risk of systemic exposure and skin irritation. In this work, previously synthesized galactosylated derivatives of common cosmetic preservatives were comparatively evaluated for transdermal permeation and preliminary toxicity. Escherichia coli β-galactosidase was used to enzymatically modify several of the commonly used cosmetic preservatives to produce their corresponding galactosylated derivatives: benzyl alcohol β-d-galactopyranoside 7, 2-phenoxyethanol β-d-galactopyranoside 8, chlorphenesin β-d-galactopyranoside 9, 1,2-hexanediol β-d-galactopyranoside 10, 1,2-octanediol β-d-galactopyranoside 11, and 2-phenylethyl β-d-galactopyranoside 12. HPLC and NMR spectroscopy were used to analyze the previously synthesized derivatives. The Franz diffusion cell assay was used to evaluate skin penetration. 2-Phenoxyethanol (PE), chlorphenesin (CPN), and 2-phenylethanol (PhE), showed measurable skin penetration, with flux values ranging from 3.82 to 7.34 µg·h−1·cm−2 and permeability coefficients (Kp) between 1.38 and 3.00 × 10−3 cm·h−1. In contrast, their galactosylated derivatives showed markedly reduced permeation under the same experimental conditions. Moreover, brine shrimp lethality assays indicated that galactosylated derivatives had significantly higher LD50 values (1.6–2.1 mg/mL) than their parent compounds (0.1–0.79 mg/mL), suggesting lower cytotoxicity. These findings suggest that enzymatic galactosylation can significantly decrease skin permeability and the toxicity of cosmetic preservatives, highlighting its potential approach to improve the safety of cosmetic components.