Oral administration of inflammatory microenvironment-responsive carrier-free infliximab nanocomplex for the targeted treatment of inflammatory bowel disease

[Display omitted] •A nanocomplex for oral administration of IFX was developed.•The nanocomplex showed extremely high drug loading and bioresponsive release.•The nanocomplex was accumulated in the inflamed tissues by HA modification.•The nanocomplex exhibit great efficacy on amelioration of colitis. Although the strategy for administering antibodies orally for inflammatory bowel disease (IBD) treatment has been proposed, the rational design for efficient delivery system is still a challenge, restricted by poor drug loading and nonspecific distribution. In this study, we developed an inflammatory microenvironment-responsive nanocomplex (IFXSS@HA or IFXTK@HA) for oral administration of Infliximab (IFX) for IBD treatment using self-cross-linking technology, which was developed by reactive oxygen species–responsive cross-linkers and fabricated with hyaluronic acid. The nanocomplex is a “carrier-free” antibody backpack with a high drug loading (>90%), inflammation targeting, and bioresponsive controlled release. The results of preliminary in vivo studies indicated that the nanocomplex showed an extended retention time and caused an increased antibody accumulation in the inflamed intestinal tissues based on hyaluronic acid functionalization and responsive controlled release within the inflammation site, exhibiting great efficacy by reducing intestinal inflammation and systemic exposure. This study provided a rational design for an oral delivery system of antibodies, explored the design of the combination of vehicle and functionalization, and showed a strategy for the oral administration of antibodies in IBD treatment.