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<p>Retinol has emerged as a star ingredient in the cosmetics industry owing to its remarkable skincare efficacy. However, its major limitations—high irritation potential and chemical instability—necessitate further improvement. We developed a liposome primarily composed of glyceryl monooleate and poloxamer (F127). By hybridizing this with a binary alcohol system comprising a 1:1 (v/v) mixture of propylene glycol and dipropylene glycol, an ethosome (ES) capable of efficiently encapsulating retinol was obtained. Retinol-loaded ES (Ret-ES) was further modified with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS@Ret-ES), thereby optimizing particle size distribution and drug loading capacity. Increasing the binary alcohol concentration from 10 to 30% caused TPGS@Ret-ES hydrated particle size to sharply decrease from 100 to 50&#xa0;nm, without significant changes in drug loading or encapsulation efficiency. Compared with retinol aqueous solutions, TPGS@Ret-ES substantially reduced degradation rates at room temperature while maintaining excellent particle size stability. Additionally, incorporating antioxidants tocopheryl acetate and Irganox 1010 further improved chemical stability. Notably, TPGS@Ret-ES simultaneously enhanced transdermal drug permeation and skin retention, with no significant irritation observed following repeated application to the same skin site in guinea pigs. In conclusion, ES represents a highly promising topical delivery carrier, and TPGS@Ret-ES shows considerable potential as a novel formulation for retinol.</p> Graphical Abstract <p></p>

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TPGS Modified Phospholipid-free and Cholesterol-free Ethosomes Enhance Chemical Stability and Transdermal Permeation Of Retinol

  • 期刊论文

  • 发表日期：

    2026年4月14日

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  • Fanjun Xu,
  • Meiting Li,
  • Hang Ruan,
  • Teng Guo,
  • Zhi Wang,
  • Nianping Feng,
  • Yongtai Zhang

摘要

Retinol has emerged as a star ingredient in the cosmetics industry owing to its remarkable skincare efficacy. However, its major limitations—high irritation potential and chemical instability—necessitate further improvement. We developed a liposome primarily composed of glyceryl monooleate and poloxamer (F127). By hybridizing this with a binary alcohol system comprising a 1:1 (v/v) mixture of propylene glycol and dipropylene glycol, an ethosome (ES) capable of efficiently encapsulating retinol was obtained. Retinol-loaded ES (Ret-ES) was further modified with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS@Ret-ES), thereby optimizing particle size distribution and drug loading capacity. Increasing the binary alcohol concentration from 10 to 30% caused TPGS@Ret-ES hydrated particle size to sharply decrease from 100 to 50 nm, without significant changes in drug loading or encapsulation efficiency. Compared with retinol aqueous solutions, TPGS@Ret-ES substantially reduced degradation rates at room temperature while maintaining excellent particle size stability. Additionally, incorporating antioxidants tocopheryl acetate and Irganox 1010 further improved chemical stability. Notably, TPGS@Ret-ES simultaneously enhanced transdermal drug permeation and skin retention, with no significant irritation observed following repeated application to the same skin site in guinea pigs. In conclusion, ES represents a highly promising topical delivery carrier, and TPGS@Ret-ES shows considerable potential as a novel formulation for retinol.

Graphical Abstract