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

Purpose Anti-aging and skin brightening are key challenges in skincare, with retinol (RET) and niacinamide (NA) being widely used for these purposes. However, RET suffers from poor stability (prone to degradation under light, oxygen, etc.), while NA exhibits limited skin permeation, restricting their efficacy. Therefore, this study aims to develop a liposomal co-delivery system (RN-Lip) to overcome these limitations, enhance the stability of RET and skin permeation of NA, and thereby improve their synergistic anti-aging and skin-brightening effects. 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. In vitro transdermal delivery, cellular uptake, cytotoxicity, and cellular efficacy tests were further carried out. Results The developed RN-Lip showed nanoscale structure, narrow size distribution, and high loading capacity. Liposomal encapsulation effectively enhancing RET stability, and considerably improve the skin retention of both ingredients. It remarkably promoted cellular uptake in B16F10, BJ cells and HaCaT cells and protected HaCaT cells from H₂O₂-induced oxidative damage. Co-administration with RET and NA exhibited synergistic effect in reducing melanin production and tyrosinase activity in B16F10 cells, while RN-Lip demonstrated superior inhibition effect compared to free ingredient. In addition, RN-Lip remarkably increased type I collagen expression in BJ cells. Conclusion RN-Lip successfully co-delivers RET and NA, overcoming their individual limitations and boosting their skincare functionality, holding significant potential for advanced anti-aging and skin-brightening applications.