Understanding the Supramolecular Chemistry of Lutein with Gelatin, Octenyl Succinic Anhydride‐Modified Starch Polymers in Simulated Gastro‐Intestinal Buffers: A Molecular Dynamics Study

Abstract Lutein, a carotenoid with significant health benefits, faces challenges in delivery due to its poor solubility and low bioavailability in the human body. Experimental methods are used to deliver lutein but it has limitations in providing detailed molecular‐level insights into lutein interactions within delivery systems. Molecular dynamics (MD) simulations offer a powerful tool to overcome this knowledge gap by providing an atomic‐level understanding of lutein behavior in various physiological conditions. This study employs MD simulations to investigate the binding of lutein in a hydrogel composed of gelatin and octenyl succinic anhydride (OSA)‐modified starch across different gastro‐intestinal buffers. The analysis of the simulation trajectory reveals that while both gelatin and OSA‐starch form hydrogel networks, OSA‐starch maintains better structural integrity in all buffers. Autodock scores indicate a higher binding affinity of lutein for OSA‐starch compared to gelatin, which is further validated by hydrogen bonding and radial distribution function analyses. The mean square displacement results demonstrate the subdiffusive behavior of lutein. These results provide valuable insights into the interactions of lutein with hydrogel components and solvents, contributing to the rational design of improved lutein delivery systems. Future research can focus on optimizing the hydrogel composition to enhance lutein stability and bioavailability in various physiological environments.