Casting New Light on the Retinol and Retinyl Palmitate Functions as Chemical Enhancers for Transdermal/Topical Drug Delivery.

Retinol and retinyl palmitate, with excellent whitening and antioxidant activities, are widely used as essential functional ingredients in transdermal preparations and skincare products. Herein, for the first time, the influence and underlying mechanisms of retinol and retinyl palmitate on the skin penetration of caffeine are investigated. It is found that the penetration of caffeine is very significantly enhanced by retinol and retinyl palmitate with 2.83 and 2.57 folds, respectively. Mechanistic studies showed that they can disrupt the lipids of intercellular orderly arrangement and reduce the content of orthorhombic lattices in the skin, making the skin loose and the barrier function decreased. Furthermore, due to the formation of chemical bonds with the skin keratin, they have a strong affinity with the skin, changing the dense secondary structure of keratin with a reduced skin barrier effect. This study provides new evidence for the potential of retinol and retinyl palmitate as novel skin penetration enhancers with high safety that possess great potential for application in the transdermal delivery of pharmaceutical and cosmetic active substances.