Preliminary In Vitro Assessment of Whey Protein Isolate Hydrogel with Cannabidiol as a Potential Hydrophobic Oral Drug Delivery System for Colorectal Cancer Therapy

Colorectal cancer (CRC) is the second global cause of cancer morbidity. Often, potent CRC drugs fail to reach the market, due to the molecule having low solubility levels. Therefore, there is a need to develop a viable, targeted delivery system for hydrophobic drugs. Whey protein isolate (WPI), in the form of hydrogels, has demonstrated loadability with hydrophobic molecules. Hydrophobic cannabidiol (CBD) has demonstrated potential in inhibiting and suppressing CRC tumour growth. Therefore, in this study, WPI hydrogels were assessed as a novel oral hydrophobic drug delivery vehicle, using CBD as a model drug. The hydrogels were analysed in conditions consistent with the alimentary tract. The investigation was performed at pH 2 (stomach), pH 7 (small intestines) and pH 9 (large intestines) and using the enzymes pepsin (stomach) and protease (small and large intestines) to simulate the digestive environment. Polymer swelling assays demonstrated that the swelling potential of the hydrogels was strongly dependent on pH. At pH 2, hydrogels decreased in mass, losing around 10% of their initial mass, while hydrogels in a pH 9 environment increased in mass by approximately 50%. However, the enzymatic degradation of the hydrogels at pH 2 (pepsin, stomach), pH 7 (protease, small intestines) and pH 9 (protease, large intestines) was more pronounced in the neutral-alkaline pH range. Pepsin at pH 2 had no significant effect on the hydrogels. In contrast, protease at pH 9 significantly degraded the hydrogels, resulting in a mass loss of 30-40% from the initial mass. The results suggesting a higher rate of degradation in the intestines rather than in the stomach. Furthermore, CBD release, analysed with U.V. spectroscopy, demonstrated a higher release rate in pH conditions associated with the intestines (pH 7 and pH 9) rather than the stomach (pH 2), suggesting a higher rate of CBD release in regions of the digestive tract affected by CRC. Significantly, the hydrogels significantly reduced the viability of HT29 CRC cells. This study demonstrates the potential of the utilisation of WPI hydrogels as an oral hydrophobic drug delivery system.