Research Highlights Retinoid Bioactivity with Moisturizer Layering Techniques

Asha Patel Shah, MD, MBA, FAAD, presented findings on the effects of layering moisturizers with retinol and tretinoin during the 2025 American Academy of Dermatology (AAD) Annual Meeting held from March 7 to 11 in Orlando, Florida. She noted that there had been no previous scientific studies examining how different layering techniques impact molecular retinoid bioactivity.

Shah, a board-certified dermatologist and adjunct assistant professor at Emory University, explained the significance of generating data to support clinical recommendations. In an interview with Dermatology Times, she addressed concerns about the potential dilution effect on retinoid treatments that may arise from layering techniques, often referred to informally as the “sandwich technique.”

The research focused on the bioactivity of retinol and tretinoin when combined with lightweight water gel and water cream moisturizers. The poster titled “Tretinoin and Retinol Bioactivity are Retained When Layered with Adjunctive Water Gel Moisturizer or A Water Cream Moisturizer in an ‘Open Sandwich’ Regimen” detailed how the team conducted an ex vivo study using human skin biopsies.

In this study, three treatment regimens were applied: a retinoid alone, an “open sandwich” (moisturizer before or after retinoid), and a “full sandwich” (moisturizer-retinoid-moisturizer). Four biopsies per treatment were analyzed using quantitative polymerase chain reaction (qPCR) to assess retinoid-induced bioactivity through gene expressions of HBEGF and HAS3.

The results indicated that explants using the “full sandwich” approach exhibited reduced bioactivity (p<0.05) measured by HBEGF gene expression, while those treated with the “open sandwich” regimen maintained bioactivity comparable to the retinoid alone.

Shah emphasized that the study's findings affirm that open sandwiching does not diminish the efficacy of retinol or tretinoin, allowing for improved patient tolerance during retinization. However, the full sandwiching method significantly lowered retinoid activity, likely due to dilution and penetration barriers. This is particularly relevant for patients with sensitive skin during initial retinoid therapy.

The tested moisturizers incorporated natural moisturizing factors and a biomimetic liquid crystal matrix, both of which enhanced skin hydration while preserving retinoid activity. These formulations were well-tolerated in patients with conditions such as acne, rosacea, atopic dermatitis, and cosmetic intolerance syndrome, reinforcing dermatologists’ ability to provide evidence-based guidelines for retinoid application techniques.

The research conducted was sponsored by Kenvue Brands, LLC.

Reference: Parsa R, Li WH, Patel R, et al. Tretinoin and retinol bioactivity are retained when layered with adjunctive water gel moisturizer or a water cream moisturizer in an “open sandwich” regimen. Poster presented at: 2025 American Academy of Dermatology Annual Meeting; March 7-11, 2025; Orlando, FL.