Division of Biology, Department of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, 2, Dublin, Ireland; School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, 2, Dublin, Ireland.
Division of Biology, Department of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, 2, Dublin, Ireland.
Eur J Pharm Sci. 2023 Apr 1;183:106379. doi: 10.1016/j.ejps.2023.106379. Epub 2023 Jan 13.
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.
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.
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.
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.
抗 TNF 生物疗法，如英夫利昔单抗（INF），彻底改变了炎症性肠病（IBD）的治疗方法。然而，由于全身给药引起的严重不良反应会显著影响患者的生活质量，限制其疗效。口服纳米药物为提供局部递送至发炎的胃肠道组织提供了一种创新的解决方案，从而限制了全身暴露并增强了治疗效果。本研究旨在研究 INF 纳米药物治疗 IBD 的潜力，重点研究纳米颗粒（NP）大小对 INF 靶向上皮屏障的调节作用。
建立了健康和炎症的体外肠道上皮屏障模型，以研究不同粒径和多分散性的 PLGA-PEGNP 的细胞相互作用。通过 INF 与 NPs 的静电相互作用制备 INF 负载的 NPs，并在炎症上皮细胞屏障模型中检查其治疗效果。
NP 相互作用在炎症细胞屏障模型中显著增强，观察到 130-300nm NPs 的转运增加，而较大 NPs（约 600nm）则在屏障处积聚。通过约 600nm NPs 将 INF 直接递送至发炎的屏障，与单独使用 INF 相比，加速了屏障完整性的恢复，并减少了炎症细胞因子的分泌和细胞毒性。
本研究结果表明，NP 粒径可用于差异靶向和治疗发炎的肠道屏障。经调制大小的口服 INF 纳米药物为 IBD 的局部、靶向治疗提供了一种新策略。
