The mucosal protein corona in local nanoparticle drug delivery

For therapeutic delivery to the gastrointestinal, ocular, respiratory, and vaginal surfaces to be effective, formulations must be engineered to overcome the protective mucus barrier. To accomplish this, nanoparticle-based formulations designed to avoid entrapment in mucus have proven to be an ideal platform to improve the retention and delivery of therapeutic cargos to mucosal tissues. However, most of the past work in this area has not considered how proteins and lipids present in the mucus matrix impact the transport, distribution, and uptake of locally delivered nanoparticles. Despite decades of research examining the protein corona formed on systemically administered nanoparticles, very little is known regarding the protein corona formation and biological identity of mucus-exposed nanomaterials. This perspective highlights recent findings as well as outstanding questions surrounding the mucosal protein corona of locally delivered nanoparticle formulations.