Biomimetic Nanocomposite Made of Ginger-derived Exosome and Inorganic-framework for high-performance Delivery of Oral Antibody

For inflammatory bowel disease (IBD) therapy, systemic exposure of anti-TNF-α antibodies brought by current clinical injection always cause serious adverse effects. Colon-targeted delivery of anti-TNF-α antibodies through oral route is of great importance but remains a formidable challenge. Here, we reported a biomimetic nanocomposite made of ginger-derived exosome and inorganic-framework for this purpose. Large-mesoporous silicon nanoparticle (LMSN) was uniquely customized for the antibody (Infliximab, INF) to high load it up to 61.3 wt % and prevent its aggregation. Exosome-like nanovesicles were isolated from ginger (GE) with a high-level production (17.5 mg·kg-1). Then, ultrasonic was used to make the GE coat onto the LMSN to obtain the biomimetic nanocomposite LMSN@GE. As expected, LMSN@GE showed advantages on oral delivery of INF: stability in gastrointestinal tract, colon-targeted delivery and high intestinal epithelium permeability. Amazingly, GEs also presented anti-inflammatory effect by blocking NLRP3 inflammasome in addition to its delivery value. As a result, the INF/LMSN@GE achieved a significant higher efficacy in colitis mice compared to the intravenously administered INF. This work brings new insights to colon-targeted delivery of anti-TNF-α antibodies via oral routes. Moreover, it puts forward a novel strategy for drug delivery by using one therapeutic ingredient (herb-derived exosome).