Co-delivering Retinol and Niacinamide via Liposomes: Enhanced Stability, Efficient Skin Permeation, and Improved Anti-Aging/Skin-Brightening Efficacy

Purpose Retinol (RET) and niacinamide (NA) are widely used in anti-aging and skin-brightening skincare products. However, RET is unstable under light and oxygen, while NA exhibits poor skin permeation. This study aimed to develop a liposomal co-delivery system (RN-Lip) to overcome these limitations and enhance the synergistic efficacy of the two compounds. Method RN-Lip was prepared by lipid film hydration, followed by extrusion to decrease particle size. The liposomal formulation was optimized, and its stability was evaluated under various conditions. Additionally, in vitro transdermal delivery, cellular uptake, cytotoxicity, and cellular efficacy evaluations were performed. Results The optimized RN-Lip exhibited a particle size of 147.03 ± 3.76 nm. The encapsulation efficiencies (EE) for NA and RET were 19.47% and 41.67%, respectively. Liposomal encapsulation improved the stability of RET, with a 7-fold higher retention rate than free RET after 30 days of storage at room temperature (under light protection). Compared to free NA and RET, liposomal encapsulation increased the skin retention of NA and RET by 3.8-fold and 1.5-fold, respectively, and further enhanced cellular uptake. Furthermore, RN-Lip reduced melanin content and tyrosinase activity in B16F10 cells compared to the free combination of RET and NA, promoted collagen I synthesis in BJ cells, and protected HaCaT cells against H₂O₂-induced oxidative damage. Conclusion RN-Lip successfully co-delivered RET and NA, overcoming their individual limitations and boosting their skincare functionalities. Thus, this system holds significant potential for advanced anti-aging and skin-brightening applications.