PEG-PLGA nanoparticles transport across in vitro intestinal epithelial models and show potential for oral delivery of antibodies in inflammatory bowel disease

Oral delivery of antibody therapies for inflammatory bowel disease (IBD) is highly desirable since it may improve the safety profile of these therapies by reducing their systemic exposure, in addition to providing convenience. Nanoparticle-based drug carriers could potentially enable oral delivery of antibodies, but most systems suffer from poor intestinal permeation. Here we tested an established polymeric nanoparticle system with a hydrophilic surface, namely polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles, for their oral delivery of adalimumab (Adb) as an exemplar antibody. Utilising an epithelial-macrophage-based co-culture model of intestinal inflammation (Caco-2/J774.A1), we show that PEG-PLGA nanoparticles of around 100 nm with slight negative zeta potential, and encapsulating Adb (28 % encapsulation efficiency) were capable of transporting the drug across the intestinal epithelial monolayers, resulting in the attenuation of inflammation in the co-culture model. Furthermore, Adb-encapsulated PEG-PLGA nanoparticles demonstrated a higher cell uptake and intestinal epithelial transport in inflammatory conditions. The work therefore demonstrates the potential of PEGylated PLGA nanoparticles for oral delivery of antibodies in IBD.