Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model
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Journal of Nanobiotechnology Open Access
RESEARCH
Nanocomposites‑based targeted oral drug delivery systems with infliximab in a murine colitis model Jung Min Kim1,2†, Da Hye Kim1,2†, Hyo Jeong Park3, Hyun Woo Ma1,2,4, I Seul Park1,2,4, Mijeong Son1,2,4, So Youn Ro3, Seokmann Hong3,5, Hyo Kyung Han6, Soo Jeong Lim3, Seung Won Kim1,2,4* and Jae Hee Cheon1,2,4*
Abstract Background: Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. Results: All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EACIFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17). Conclusion: We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD. Keywords: Inflammatory bowel disease, Infliximab, Nanocomposite carrier, Oral delivery system Background Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition of the gastrointestinal tract. Cytokines are essential mediators of IBD pathophysiology *Correspondence: [email protected]; [email protected] † Jung Min Kim and Da Hye Kim contributed equally to this work 1 Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50‑1 Yonsei‑ro, Seodaemun‑gu, Seoul 03722, Republic of Korea 4 Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50‑1 Yonsei‑ro, Seodaemun‑gu, Seoul 03722, South Korea Full list of author information is available at the end of the article
and tumor necrosis factor (TNF)-α has a crucial function in the initiation and perpetuation of IBD [1]. TNF-α alters epithelial integrity, disrupts barrier function, and promotes the breakdown of intestinal homeostasis [2]. Moreover, the binding of TNF-α to the TNF receptor is associated with the prevention of apoptosis and prolongation of pro-inflammatory T cell survival in IBD [3]. Increased blood monocyte recruitment into the gut of IBD patients generates macrophages that leads to the secretion of infla
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