Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model

基于纳米复合材料的英夫利昔单抗靶向口服药物输送系统在小鼠结肠炎模型中的应用

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作者:Jung Min Kim, Da Hye Kim, Hyo Jeong Park, Hyun Woo Ma, I Seul Park, Mijeong Son, So Youn Ro, Seokmann Hong, Hyo Kyung Han, Soo Jeong Lim, Seung Won Kim, Jae Hee Cheon2

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.

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.

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, and Il17).

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