Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 18, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12951-020-00693-4
Keywords
Inflammatory bowel disease; Infliximab; Nanocomposite carrier; Oral delivery system
Funding
- Korea Health Technology RAMP
- D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health AMP
- Welfare, Republic of Korea [HI18C0094]
- Korea Health Promotion Institute [HI18C0094010019] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Background: Infliximab (IFX), a TNF-alpha 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 EAC-IFX-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, andIl17). 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.
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