Caffeic acid phenethyl ester loaded in nano-targeted delivery system with casein: Physicochemical characterization, in vitro release, and binding mechanisms

Abstract Caffeic acid phenethyl ester (CAPE) is a phenolic substance with beneficial biological activities. However, low water solubility and bioavailability limit its applications. In this study, a nanoscaled targeted delivery system for CAPE was constructed using casein, sodium alginate (NaAlg), and Ca2+. The physicochemical properties, encapsulation efficiency, and morphology of the nanoparticles were characterized. The pH and storage stability, in vitro release rate, and the binding mechanisms between CAPE and casein were investigated. The results showed that Ca-casein-CAPE-NaAlg nanoparticles had a uniform particle size (211 ± 5.1 nm), high encapsulation efficiency (96 ± 3.98%) and loading capacity (7.01%). Fourier-transform infrared spectroscopy (FT-IR) and circular dichroism (CD) analysis confirmed the combination of CAPE and casein via hydrophobic interaction. The nanoparticles remained stable in pH 5.5–7.0 and storage at room temperature for 4 weeks. The nanoparticles effectively prevented digestion of CAPE by pepsin in vitro. Hydrophobic interactions were the main force that maintained the binding of CAPE and casein. The molar ratio of CAPE to casein in the nanoparticles was approximately 7.72–8.36:1. Therefore, the newly developed nanoparticles are expected to form delivery systems that could effectively improve the stability and bioavailability of low water-soluble bioactive compounds for applications in the functional foods and dietary supplements.