pH-Responsive Polymeric Nanoparticles for the Oral Delivery of High Isoelectric Point Therapeutic Proteins

摘要

Replacing the pH-responsive monomer methacrylic acid with itaconic acid doubles the number of charged groups on each repeat unit while otherwise minimally changing the polymeric structure. This change leads to increased swelling compared to the methacrylic acid-based system and thus larger mesh size, allowing the protein to be released more readily from the nanogels. This platform shows potential for the delivery of high pI proteins, but further studies are required before pursuing clinical use. The loaded nanoparticles will be tuned for improved transepithelial transport properties before being evaluated in vitro using a Caco-2 and HT29-MTX co-culture model for the intestinal epithelium. Low cytotoxicity will be confirmed with an MTS assay and protein transport studies will be conducted across the model epithelial membrane. Finally, the system will be evaluated with a murine model to test its in vivo efficacy.