Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Przybyszewskiego Street 49, 60-355, Poznan, Poland.
Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznan, Poland.
J Nanobiotechnology. 2021 Oct 29;19(1):346. doi: 10.1186/s12951-021-01090-1.
Despite significant advances in therapeutic possibilities for the treatment of inflammatory bowel disease (IBD) in recent years, there is still a big room for improvement. In particular, biological treatment can induce not only clinical remission but also mucosal healing of the gastrointestinal tract. Among these therapeutic molecules, anti-tumor necrosis factor-alpha (anti-TNF-α) antibodies were the first to revolutionize treatment algorithms in IBD. However, due to the parenteral route of administration and systemic mode of action, TNF-α blockers are characterised by high rates of immunogenicity-related loss of response and serious adverse events. Moreover, intravenous or subcutaneous therapy is not considered patient-friendly and requires occasional, direct contact with healthcare centres. To overcome these limitations, several attempts have been made to design oral pharmaceutical formulations of these molecules. It is hypothesized that oral anti-TNF-α antibodies therapy can directly provide a targeted and potent anti-inflammatory effect in the inflamed gastrointestinal tissues without significant systemic exposure, improving long-term treatment outcomes and safety. In this review, we discuss the current knowledge and future perspectives regarding different approaches made towards entering a new era of oral anti-TNF-α therapy, namely, the tailoring of biocompatible nanoparticles with anti-TNF-α antibodies for site-specific targeting to IBD. In particular, we discuss the latest concepts applying the achievements of nanotechnology-based drug design in this area.
尽管近年来在治疗炎症性肠病（IBD）方面的治疗可能性方面取得了重大进展，但仍有很大的改进空间。特别是，生物治疗不仅可以诱导临床缓解，还可以诱导胃肠道的黏膜愈合。在这些治疗分子中，抗肿瘤坏死因子-α（anti-TNF-α）抗体是第一个彻底改变 IBD 治疗方案的药物。然而，由于给药途径和全身作用模式，TNF-α 阻滞剂的特点是与免疫原性相关的应答丧失率高，并且会发生严重的不良反应。此外，静脉或皮下治疗被认为不便于患者使用，并且需要偶尔直接与医疗中心联系。为了克服这些局限性，已经进行了多次尝试来设计这些分子的口服药物制剂。人们假设口服抗 TNF-α 抗体治疗可以直接在炎症胃肠道组织中提供靶向且有效的抗炎作用，而不会产生显著的全身暴露，从而改善长期治疗效果和安全性。在这篇综述中，我们讨论了关于进入口服抗 TNF-α 治疗新时代的不同方法的现有知识和未来展望，即通过将抗 TNF-α 抗体与生物相容性纳米颗粒结合来进行针对 IBD 的靶向给药。特别是，我们讨论了在这一领域应用基于纳米技术的药物设计的最新概念。
