Enhanced Stability and Oral Bioavailability of Cannabidiol in Zein and Whey Protein Composite Nanoparticles by a Modified Anti-Solvent Approach

Wide applications of cannabidiol (CBD) in the food and pharmaceutical industries are limited due to its low bioavailability, sensitivity to environmental pressures and low water solubility. Zein nanoparticles were stabilized by whey protein (WP) for the delivery of cannabidiol (CBD) using a modified anti-solvent approach. Particle size, surface charge, encapsulation efficiency, and re-dispersibility of nanoparticles were influenced by the zein to WP ratio. Under optimized conditions at 1:4, zein-WP nanoparticles were fabricated with CBD (200 μg/mL) and further characterized. WP absorbed on zein surface via hydrogen bond, hydrophobic forces, and electrostatic attraction. The zein-WP nanoparticles showed excellent storage stability (4 °C, dark) and effectively protected CBD degradation against heat and UV light. In vivo pharmacokinetic study demonstrated that CBD in zein-WP nanoparticles displayed 2-times and 1.75-fold enhancement in maximum concentration (C max) and the area under curve (AUC) as compared to free-form CBD. The data indicated the feasibility of developing zein-WP based nanoparticles for the encapsulation, protection, and delivery of CBD.