An Innovative Dendrimer-Based Retinol Delivery System for Xerosis Care: Stability, Tolerance, and Sustained Hydration

Background: Retinol is a mainstay of dermatological care due to its central role in epidermal differentiation, skin barrier repair, and tissue regeneration. However, its clinical use is limited by poor physicochemical stability, rapid photodegradation, and frequent skin intolerance, particularly in individuals with impaired skin barrier function. Supramolecular biovectorization strategies could overcome these limitations. Objectives: This study aimed to evaluate the impact of third-generation dendritic poly-L-lysine (PLL_G3; 22 kDa, ~7 nm) on retinol stability, skin tolerance, and skin functional performance. Methods: A supramolecular retinol-poly-L-lysine complex was characterized in terms of encapsulation efficiency and physicochemical stability using HPLC and UV spectroscopy under oxidative, thermal, and photochemical stress. The stability of the formulation was evaluated as hydrophilic emulsion over a three-month period. Skin functional efficacy was evaluated by corneometric analysis of stratum corneum hydration after topical application, as well as by clinical assessment of tolerance and efficacy after repeated daily use over 28 days in subjects presenting xerosis, defined as dry to very dry skin. Results: Retinol remained structurally intact in the PLL_G3 matrix, confirming a reversible, non-covalent encapsulation mechanism. The formulation exhibited high physicochemical stability, with only minimal changes after prolonged UV exposure. Corneometric measurements showed a rapid and sustained increase in skin hydration, reaching +61.5% two hours after application. After 28 days of repeated use, the formulation was well tolerated, with no signs of irritation or sensitization, and demonstrated significant improvements in skin dryness, suppleness, and comfort. Conclusions: PLL_G3-based supramolecular vectorization significantly improves stability, tolerance, and functional hydration of the skin by retinol. By enabling controlled release while preserving the integrity of the epidermal barrier, poly-L-lysine dendrimers represent a clinically relevant strategy for safer and more effective topical use of retinol, particularly on sensitive, xerotic, inflammatory, and photoaged skin.