Transport and Delivery of Interferon-α Through Epithelial Tight Junctions via pH-Responsive Poly(Methacrylic Acid Grafted Ethylene Glycol) Nanoparticles.

Whereas significant advancements have been made in our fundamental understanding of cancer, they have not yet translated into effective clinical cancer treatments. One of the areas that has the potential to improve the efficacy of cancer therapies is the development of novel drug delivery technologies. In particular, the design of pH-sensitive polymeric complexation hydrogels may allow for targeted oral delivery of a wide variety of chemotherapeutic drugs and proteins. In this work, poly(methacrylic acid grafted ethylene glycol) (P(MAA-g-EG) hydrogel nanoparticles were synthesized, characterized, and studied as matrix-type, diffusion-controlled, pH-responsive carriers to enable the oral delivery of the chemotherapeutic agent Interferon Alpha (IFN-α). The biophysical mechanisms controlling the transport of IFN-α were investigated using a Caco-2/HT29-MTX co-culture as a gastrointestinal (GI) tract model. The synthesized nanoparticles exhibited pH-responsive swelling behavior and allowed the permeation of IFN-α through the tight junctions of the developed cellular gastrointestinal epithelium model. These studies demonstrate the capabilities of these particles to contribute to the improved oral delivery of protein chemotherapeutics.