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    Oral delivery of anti-TNF antibody shielded by natural polyphenol-mediated supramolecular assembly for inflammatory bowel disease therapy

    Xinyu Wang, Junjie Yan,Lizhen Wang,Donghui Pan, Yuping Xu, Fang Wang, Jie Sheng, Xinxin Li, and Min Yang
    Theranostics. 2020; 10(23): 10808–10822.

    Rationale: Anti-tumor necrosis factor (TNF) therapy is a very effective way to treat inflammatory bowel disease. However, systemic exposure to anti-TNF-α antibodies through current clinical systemic administration can cause serious adverse effects in many patients. Here, we report a facile prepared self-assembled supramolecular nanoparticle based on natural polyphenol tannic acid and poly(ethylene glycol) containing polymer for oral antibody delivery. Method: This supramolecular nanoparticle was fabricated within minutes in aqueous solution and easily scaled up to gram level due to their pH-dependent reversible assembly. DSS-induced colitis model was prepared to evaluate the ability of inflammatory colon targeting ability and therapeutic efficacy of this antibody-loaded nanoparticles. Results: This polyphenol-based nanoparticle can be aqueous assembly without organic solvent and thus scaled up easily. The oral administration of antibody loaded nanoparticle achieved high accumulation in the inflamed colon and low systemic exposure. The novel formulation of anti-TNF-α antibodies administrated orally achieved high efficacy in the treatment of colitis mice compared with free antibodies administered orally. The average weight, colon length, and inflammatory factors in colon and serum of colitis mice after the treatment of novel formulation of anti-TNF-α antibodies even reached the similar level to healthy controls. Conclusion: This polyphenol-based supramolecular nanoparticle is a promising platform for oral delivery of antibodies for the treatment of inflammatory bowel diseases, which may have promising clinical translation prospects. Keywords: Supramolecular nanoparticles, oral delivery, polyphenol, anti-TNF therapy, inflammatory bowel disease

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