Background and aims: Anti-TNF biological therapies such as infliximab (INF) have revolutionised the treatment of inflammatory bowel diseases (IBD). However, serious adverse effects due to systemic administration can significantly impact patient quality of life, limiting their success. Oral nanomedicines propose an innovative solution to provide local delivery to inflamed gastrointestinal tissues, thereby limiting systemic exposure and enhancing therapeutic efficacy. This study aimed to examine the potential of INF nanomedicines for IBD treatment with a focus on nanoparticle (NP) size to modulate the targeting of INF to the epithelial barrier.
Methods: Healthy and inflamed in vitro models of the intestinal epithelial barrier were established to examine the cell interaction of PLGA-PEGNPs of varying particle sizes and polydispersities. INF-loaded NPs were prepared by electrostatic interaction of INF with NPs and examined for their therapeutic efficacy in the inflamed epithelial cell barrier model.
Results: NP interaction was significantly enhanced in the inflamed cell barrier model, with increased transport observed for 130 - 300 nm NPs and accumulation of larger NPs (∼600 nm) at the barrier. Delivery of INF directly to the inflamed barrier by ∼600 nm NPs accelerated recovery of barrier integrity and reduced inflammatory cytokine secretion and cytotoxicity in comparison to treatment with INF alone.
Conclusions: Results from this study show that NP particle size can be used to differentially target and treat the inflamed intestinal barrier. Oral INF nanomedicines of modulated size present a novel strategy for the local, targeted treatment of IBD.
Keywords: Caco-2 cells; Inflammatory bowel disease; Infliximab; Nanoparticles; Oral targeted delivery; PLGA-PEG.
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