Development of New Anti-Cancer WPI Hydrogels with a Long-Term pH-Dependent Drug Release Profile

Abstract

Recently, much attention has been paid to hydrogels in drug delivery. In this regard, hydrogels must comply with principles such as biocompatibility, biodegradation, and non-toxicity. Whey Protein Isolate (WPI) is one common protein-based formulation used to form hydrogels in the food industry. Whey proteins have been found to have desirable gelling properties because they are composed of branched-chain amino acids that promote the formation of highly hydrated three-dimensional polymer networks in hydrogels. An important functional property of WPI hydrogels is their high ability to retain water or biological fluids in their structure. Cytocompatible hydrogels have been used successfully to develop drug delivery systems because of their stimulus-sensitive response to external triggers such as pH. Hence, it would be desirable to combine the ability of WPI hydrogels to solubilize and carry hydrophobic drugs with pH responsiveness. In this study, we combined the beneficial properties of tannin acids (TA) and WPI to create novel pH-sensitive cytocompatible hydrogels that have anti-cancer effects. We hypothesized that the addition of TA would reduce the swelling of WPI hydrogels due to intermolecular interactions between polyphenols and proteins. This combination of ingredients has not yet been tested for biomaterial applications to the best of our knowledge. We focused on the dependence of the swelling capacity of hydrogels on the pH, chemical structure, and TA concentration, which allowed a longer TA release over several days. The behavior of hydrogels sensitive to external pH is especially useful in the development of anti-cancer scaffolds. The greatest influence on the change in swelling is exerted by the amount of TA contained in WPI hydrogels. Increasing the TA / WPI ratio in hydrogels to 0.30 results in a significant decrease in swelling rate (SR) compared to the control hydrogel without TA under neutral conditions (pH 7). A decrease in pH leads to a decrease in SR and an increase in the amount of released TA by a factor of 1.5–2 compared to incubation at pH 7 for all WPI hydrogels with and without TA. The maximum TA release was observed for hydrogels with a minimum TA content (TA / WPI 0.0375) at pH 9 and was almost 80% 48 h after the incubation start. According to the swelling data, hydrogels begin to degrade at this point in time since their MI after 48 h has negative values. All obtained hydrogels containing TA have cytotoxic properties against the Hep-2 cell line of human laryngeal carcinoma (Hep-2). An increase in the concentration of TA in hydrogels leads to an increase in the cytotoxic effect. Thus, WPI hydrogels can be used as anti-cancer scaffolds with a prolonged TA release profile.

This work was supported by the Russian Science Foundation (project no. 21-75-10042).

Speaker

Mayorova Oksana A.
Saratov State University
Russia

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