Transport and delivery of interferon-α through epithelial tight junctions via pH-responsive poly(methacrylic acid-grafted-ethylene glycol) nanoparticles

Abstract

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) hydrogel nanoparticles were synthesised, characterised, 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 synthesised nanoparticles exhibited pH-responsive swelling behaviour and allowed the permeation of IFN-α through the tight junctions of the developed cellular GI epithelium model. These studies demonstrate the capabilities of these particles to contribute to the improved oral delivery of protein chemotherapeutics.

Keywords:

• Responsive hydrogels
• pH-sensitive hydrogel nanoparticles
• interferon alpha (IFN-α)
• GI tract delivery systems
• Caco-2 cell lines

Acknowledgements

This work is dedicated to Professor Patrick Couvreur of the University of Paris-Sud who has been an academic and personal friend of Prof. N. A. Peppas since 1980.

We are honouring Patrick Couvreur for his sustained and outstanding scientific achievements in drug delivery and targeting and we rejoice on his recognition by the Journal’s Lifetime Achievement Award for 2019. Since the publication in 1988 of their work on alginate magnetic releasing systems, Drs. Couvreur and Peppas have worked on the development and improvement of systems for protein delivery using a range of administration routes. Congratulations for 40 years of great research.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported in part by a grant from the US National Institutes of Health (NCI, Center for Oncophysics Grant CTO PSOC U54-CA-143837) and by the Pratt Foundation and the Cockrell Foundation.