Marwa H.S. DawoudAbdelrahman E. GhariebAhmed H.M. HassanOmaima M.B. HendawyHeba H. Awad2025-06-142025-06-142025-06-02Dawoud, M. H., Gharieb, A. E., Hassan, A. H., Hendawy, O. M., & Awad, H. H. (2025). Innovative Natural Anti-Aging Nanofiber Facial Mats: harnessing quality by design and artificial intelligence for sustainable skincare solutions. Journal of Drug Delivery Science and Technology, 107130. https://doi.org/10.1016/j.jddst.2025.107130https://doi.org/10.1016/j.jddst.2025.107130https://repository.msa.edu.eg/handle/123456789/6439SJR 2024 0.817 Q1 H-Index 89The growing emphasis on skin health among aging population has sparked attention to combat aging. Cosmeceutical products with natural ingredients provide safe, effective, and sustainable formulation with demand for clean and organic skincare. Pomegranate and collagen have emerged as promising antiaging agents, which could be easily incorporated into electrospun biodegradable nanofibers (ESN), especially if incorporated with chitosan. This study aims to formulate ESN loaded with these natural antiaging agents, using Quality by Design (QbD), complemented by artificial intelligence (AI) to predict the nanofiber diameter. A complete risk assessment study was conducted, where screening of the electrospinning solution for viscosity, surface tension, pH, and electrical conductivity to ensure optimal electrospinning conditions. The solution showed an optimal viscosity of 330.87 mPa s, surface tension of 41.76 dyne/cm, and electrical conductivity of 10004.78 μs/cm. The electrospinning process was meticulously optimized, with a flow rate of 0.2 mL/h, a voltage of 25 kV, 40 % humidity, and a needle-to-collector distance of 15 cm. An AI model was employed to predict the nanofiber diameter, demonstrating exceptional predictive accuracy. The formulated pomegranate and collagen nanofibers mat was tested in-vivo and showed significant antioxidant, anti-inflammatory, and tissue-regenerative properties, restoring SOD and collagen levels, reducing MMP-1, COX-2, and PGE-2 levels, and effectively attenuating NF-κB activation, highlighting the therapeutic potential of the formulated mats for managing skin aging. This study provides novel insights into the integration of QbD and AI for the development of natural product-based formulations, paving the way for their application in advanced pharmaceutical and cosmeceutical systems. © Elsevier B.Ven-USAntiagingCollagenElectrospun biodegradable nanofibersPomegranateArticlehttps://doi.org/10.1016/j.jddst.2025.107130