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

Kalev Freeman,Ce Wang,Yonghai Sun,Cuina Wang,Monique Alyssa Mchenry,Mingruo Guo,Jia Wang

doi:10.3390/foods11030376

Kalev Freeman, Ce Wang + Show 5 more

Open Access

https://doi.org/10.3390/foods11030376

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Abstract

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.

Highlights

Cannabidiol (CBD), a major non-psychotropic constituent of the Cannabis sativa plant, has biological activities such as anti-convulsive, anti-anxiety, anti-psychotic activity [1]
The particle size was significantly increased in CBD/zein–whey protein (WP) by comparison with CBD/zein (p < 0.05), attributed to the fact that WP was absorbed in the core due to the hydrophobic effect and electrostatic interaction
With increasing WP concentration, the particle size of composite nanoparticles significantly decreased with changing zein:WP ratios from 1:2 to 1:3, and increased (1:4 and 1:5), p < 0.05

Summary

Introduction

Cannabidiol (CBD), a major non-psychotropic constituent of the Cannabis sativa plant, has biological activities such as anti-convulsive, anti-anxiety, anti-psychotic activity [1]. The consequent zein–whey protein core–shell nanoparticles were documented to remarkably enhance the solubility, re-dispersibility, stability, and oral bioavailability of encapsulated active substances in comparison with pure zein [10,11,12]. ASP is used to introduce organic zein solution drop by drop into an antisolvent, which is time-consuming and difficult to scale up in practical application To solve this problem, a modified easy-operating anti-solvent procedure was developed by directly pouring the aqueous solution into an organic zein solution [13,14] which can encapsulate bioactive ingredients into the core. A CBD loaded zein–whey protein composite delivery system was fabricated using the modified ASP and characterized for its physicochemical properties, stability, and bioavailability

Materials

Fabrication of CBD-Loaded Composite Nanoparticles

Particle Size and Zeta-Potential

Water Solubility

2.11. Stability

2.12. In Vivo Bioavailability Study

2.13. Statistical Analysis

Re-Dispersibility of Freeze-Dried Composite Nanoparticles

XRD Diffractogram

FT-IR Spectra

Microstructure Observed by TEM

Physicochemical Stability