Encapsulation of Ferulic Acid in Lipid Nanoparticles as Antioxidant for Skin: Mechanistic Understanding through Experiment and Molecular Simulation

Ferulic acid, though used in formulations of skin-care and cosmetic products, suffers from the problems of poor stability and low aqueous solubility. Encapsulation into nanoparticles can be a viable route to overcome these inherent problems. In this proof-of-concept, we combine experimental studies and molecular dynamics (MD) simulations to provide insights into the underlying formation mechanism of ferulic acid-loaded lipid based nanoemulsion and nanoparticle formulations in aqueous environment. This experimental-cum-simulation study provides molecular-level understanding into lipid-active nanoparticle systems and would assist with the design and optimization of formulation systems for skin-care/cosmetic/pharmaceutical applications. The examined lipid is Gelucire 50/13, which is selected due to higher solubility of ferulic acid in molten Gelucire 50/13 compared to other tested lipids. Experimental results show the successful formation of nanoemulsion and subsequently nanoparticle in water with 0.5 wt % ferulic acid. While providing useful insights into structural, energetic, and dynamical properties of nanoemulsion/nanoparticle, MD simulations demonstrate that ferulic acid molecules are present at the surface layer of the nanoparticle whereas hydrophobic parts of lipid molecules exist in the core and hydrophilic parts at the surface of the nanoparticle. The nanoemulsion is originated by quick assembly of lipid molecules into many small nuclei which latter aggregate into larger clusters of spherical shape. During cooling, the shape and size of the nanoparticle are found to be unchanged, but dynamics/mobility of the nanoparticle as well as ferulic acid reduced significantly due to solidification. Additionally, higher concentrations of ferulic acid (1 or 5 wt %) lead to either the existence of unencapsulated ferulic acid in bulk or the destabilization of the nanoparticle structure, validated by experiments. Hence, the optimal concentration of ferulic acid for successful formation of nanoparticle is 0.5 wt %. Ferulic acid loaded nanoparticle can be useful for skin-care/cosmetics products.