Abstract
BackgroundInfliximab (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.ResultsAll 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).ConclusionWe 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.
Highlights
Infliximab (IFX), a tumor necrosis factor (TNF)-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD)
Characterization and gastrointestinal stability of nanocomposite carriers Transmission electron microscopy images showed that bovine serum albumin-fluorescein isothiocyanate (BSAFITC) coated with liposome-coated BSA (BSA-liposome), Aminoclay-liposome-coated BSA (AC-BSA-L), and Eudragit S100-liposome-coated BSA (EAC-BSA-L) were spherical and surrounded the inner aqueous core containing BSA-FITC (Fig. 1a)
All three nanocomposite carriers loaded with IFX were prepared with narrow size distribution and high encapsulation efficiency
Summary
Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. Therapeutic monoclonal antibodies against TNF-α are used to treat IBD [5, 6]. Infliximab (IFX) is a mouse/human chimeric monoclonal immunoglobulin G1 (IgG1) antibody against TNF-α. It directly neutralizes the biological activity of TNF-α. IFX is more effective at inducing clinical remission of IBD and mucosal healing than conventional drugs [7, 8]. An anti-TNF antibody therapy for IBD would be delivered directly to the intestinal inflammatory sites, avoiding systemic exposure and immunosuppression
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