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September 17, 2025Pharmaceuticals2 citationsOpen Access

Self-Assembly 4-Butylresorcinol Deep Eutectic Solvent Nanoparticles for Efficient Transdermal Delivery and Whitening

HHHongtao HanShenzhen Technology University DHDan HuElectric Power Research Institute YDYuanlong DengShenzhen Institute of Information Technology

Key Points

The self-assembled nanoparticles showed a 3.46-fold increase in skin permeability, enhancing transdermal delivery.
There was a 1.55-fold increase in melanin inhibition in B16 cells, highlighting the whitening effect of the formulation.
The novel 4-butylresorcinol deep eutectic solvent system presented a significant improvement in stability over traditional formulations.
These findings indicate the potential of combining self-assembly technology with deep eutectic solvents for advanced skincare.

Abstract

Background: Skin whitening agents often face challenges such as poor stability and low permeability. To overcome these issues, a novel 4-butylresorcinol (4-BR)/D-a- Tocopherol Polyethylene Glycol Succinate (TPGS) deep eutectic solvent (DES) system was developed, which can self-assemble into carrier-free nanoparticles (NPs). Methods: The 4-BR/TPGS DES was synthesized and characterized by theoretical calculations, DSC, FTIR, 1H-NMR, and 2D NMR to confirm its successful formation. Results: The self-assembled 4-BR/TPGS DES NPs showed a 3.46-fold increase in skin permeability, a 1.53-fold improvement in 4-BR stability, a 1.55-fold increase in melanin inhibition in B16 cells, and a 2.16-fold higher melanin suppression in zebrafish compared with traditional 4-BR oil-based formulations. These results indicated the excellent whitening efficacy and transdermal delivery potential of this formulation. Conclusions: The combination of TPGS-based DES and self-assembly technology represents a revolutionary approach for advanced transdermal delivery and the development of skin care products.

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