Oral delivery of infliximab via self-assembled nano-in-microspheres for enhanced inflammatory bowel disease therapy.

Infliximab (IFX), an anti-tumor necrosis factor-alpha (anti-TNF-α) monoclonal antibody, exhibits significant therapeutic efficacy in inflammatory bowel disease (IBD). Nevertheless, systemic administration, the current clinical standard for IFX delivery, is associated with poor access to its targets and severe adverse reactions. Although nanotechnology has been reported for the oral administration of antibody, its clinical application remains limited by inadequate drug-loading capacity and poor stability. In this study, we constructed negatively charged IFX-loaded nanocomplexes using tannic acid (TA), carboxymethyl chitosan (CMC), and DSPE-MPEG2000 for oral delivery. Formed via hydrogen bonding and hydrophobic interactions, these nanocomplexes exhibit a high drug-loading efficiency (>85%) and enable targeted delivery to inflamed sites. To further enhance gastrointestinal stability, the nanocomplexes were encapsulated in alginate microspheres, which effectively prevented the premature rapid release of drugs. In vivo experimental results demonstrated that oral administration of this IFX formulation in colitis-induced mice significantly reduced the levels of pro-inflammatory cytokines (TNF-α and IL-6) and myeloperoxidase (MPO), and effectively alleviated colonic tissue damage. This IFX formulation exhibits excellent potential for oral antibody delivery, with enhanced targeting efficiency and reduced systemic toxicity, thus promising to provide a novel clinically translatable strategy for IBD treatment.