Encapsulation of Peanut Allergens with Bimetallic Metal-Phenolic Networks (MPNs) for Therapeutic Applications

Abstract

The efficacy and safety of oral immunotherapy for food allergy is still an ongoing challenge. Plant-derived polyphenols have been shown to exhibit immunomodulatory action through their anti-inflammatory and antioxidant properties. This thesis explored a synthesis of dual-functional pH-responsive metal-phenolic networks (MPNs) encapsulated peanut allergens using plant phenolics as an immunomodulating “adjuvant”. The compatibility of ferric/ferrous (Fe3+/Fe2+) and zinc ion (Zn2+) with plant-derived phenolics, tannic acid (TA) and catechin hydrate (CTC), was investigated for the formation of stable MPN film and encapsulation of peanut crude protein. Using bovine serum albumin (BSA) as a template biomolecule, it was demonstrated that the concentration/molar ratio between different metal ions and between metal ions and phenolics, order of reagent addition, synthesis methods and pH change during the synthesis influenced the final colour, size, and overall surface charge of the particles. The optimum condition for each tested MPN system with the protein template tested varied significantly. In the two bimetallic systems, Fe3+ showed the strongest interaction with the other coordinating ions, and with phenolics, followed by Fe2+ and then Zn2+. The morphological and elemental analysis of the BSA-Fe2+/Zn2+-CTC MPN confirmed the spherical particles presented in clusters and that a significantly higher Fe2+ than Zn2+ presented in the bimetallic MPN system. The selected bimetallic Fe2+/Zn2+-CTC MPN was implemented in the encapsulation of peanut crude protein with mixed molecular weight (MW) proteins and the major allergen, Ara h 1. More negatively charged nanoparticles were observed for the crude protein capsules compared to Ara h 1 capsules. The pH-responsive controlled release of the crude peanut-MPN capsules under the simulated gastric condition revealed that protein-MPN capsules with final pH of 6.3 were more stable than those with pH 3.9. The former had small amounts of residues remaining intact, whilst the latter dissociated completely after 2 hr digestion. The MPN capsules disassembled immediately after being exposed to the acidic condition and the dissociation rate was faster at pH 2 than pH 3. The released peanut protein was still immunoreactive. The pH-responsive peanut-MPN capsules using the bimetallic system with immunomodulating plant polyphenols could be a prospective allergen delivery system for oral immunotherapy