Department of Microbiology and Immunology, Center for Microbiomics, Inflammation and Pathogenicity, UofL-Brown Cancer Center, University of Louisville, Louisville, KY, USA.
Institute for Stem Cell Science and Regenerative Medicine (DBT-inStem), GKVK campus, Bellary Road, Bangalore, 560065, Karnataka, India.
J Nanobiotechnology. 2024 Nov 13;22(1):701. doi: 10.1186/s12951-024-02990-8.
Inflammatory bowel disease (IBD) treatment often involves systemic administration of anti-inflammatory drugs or biologics such as anti-TNF-α antibodies. However, current drug therapies suffer from limited efficacy due to unresponsiveness and adverse side effects. To address these challenges, we developed inflammation-targeting nanoparticles (ITNPs) using biopolymers derived from the gum kondagogu (Cochlospermum gossypium) plant. These ITNPs enable selective drug delivery to inflamed regions, offering improved therapeutic outcomes. We designed ITNPs that specifically bind to inflamed regions in both human and mouse intestines, facilitating more effective, uniform, and prolonged drug delivery within the inflamed tissues. Furthermore, we demonstrated that oral administration of ITNPs loaded with urolithin A (UroA), a microbial metabolite or its synthetic analogue UAS03 significantly attenuated chemical- and immune checkpoint inhibitor- induced colitis in pre-clinical models. In conclusion, ITNPs show great promise for delivering UroA or its analogues while enhancing therapeutic efficacy at lower doses and reduced frequency compared to free drug administration. This targeted approach offers a potential solution to enhance IBD treatment while minimizing systemic side effects.
炎症性肠病（IBD）的治疗常涉及全身性抗炎药物或生物制剂的应用，如抗 TNF-α 抗体。然而，由于药物无应答和不良反应，目前的药物治疗存在疗效有限的问题。为了解决这些挑战，我们使用源自昆士兰肉豆蔻（Cochlospermum gossypium）植物的生物聚合物开发了靶向炎症的纳米颗粒（ITNPs）。这些 ITNPs 能够选择性地将药物递送到炎症部位，从而提供更好的治疗效果。我们设计了 ITNPs，使其能够特异性地结合人肠道和鼠肠道中的炎症部位，从而在炎症组织中实现更有效、更均匀和更持久的药物递送。此外，我们证明，负载乌洛托品 A（UroA）的 ITNPs 的口服给药，一种微生物代谢物或其合成类似物 UAS03，可显著减轻临床前模型中的化学和免疫检查点抑制剂诱导的结肠炎。总之，与游离药物给药相比，ITNPs 在递送 UroA 或其类似物的同时，以更低的剂量和更频繁的频率增强治疗效果，具有很大的应用前景。这种靶向方法提供了一种潜在的解决方案，可增强 IBD 的治疗效果，同时最大限度地减少全身副作用。
