Patel Alka, Jain Parag
Department of Pharmacy, Rungta College of Pharmaceutical Sciences and Research, Bhilai, Chhattisgarh, 490024, India.
Department of Pharmacy, Rungta International Skills University, Bhilai, Chhattisgarh, 490024, India.
Inflammopharmacology. 2025 Aug 15. doi: 10.1007/s10787-025-01906-8.
Ulcerative colitis (UC) is a chronic, relapsing form of an inflammatory bowel disease characterized by epithelial barrier dysfunction, immune dysregulation, and gut microbiota imbalance. Despite advances in immunosuppressive and biologic therapy, shortcoming in barrier repair and long-term remission indicate that new treatments are required. The present study aimed to determine the contribution of protein-peptide complexes to the protection against the disruption of the barrier and colonic stress in UC. It seeks to review the mode of action, pharmacokinetic limitations, and therapeutic benefits that may be gained from using peptides as the intervention rather than using the conventional techniques. A literature review and synthesis of recent data on molecular pathophysiology, clinical pharmacology, and advances in drug delivery was performed. Mechanistic models of epithelial regeneration, immune cell targeting, and reconstitution of the microbiome were summarized. Protein-peptide complexes showed broad ranges of effect including epithelial healing, immunosuppression, and microbiota control. Improvement in the tight junction value and the epithelial proliferation by GLP-2 analogs and AMP conjugated the peptides. Combined decrease in pro-inflammatory cytokines (TNF-α, IL-13, IL-17) by cell-penetrating peptides and IL-pathway inhibitors was seen. Hybrid immunomodulatory peptides for immune promotion, regulation of inflammatory macrophage, and Th1-biased immunomodulation of naïve T cells were assessed. Gut-targeted nano-carrier and pH-responsive systems were shown to enhance bioavailability and site-specific delivery of peptide. Co-delivery of peptides and biologics resulted in enhanced clinical scores in preclinical UC models. Protein-peptide complexes are a potential class of bioactive molecules, which could tackle fundamental pathophysiological derangements in UC. Their accuracy to target, low systemic toxicity, and potential for mucosal healing place them among the next generation of therapeutics. On-going translational efforts should combine peptide engineering, nanotechnology, and patient stratification for maximum clinical impact in UC management.
溃疡性结肠炎（UC）是一种慢性复发性炎症性肠病，其特征为上皮屏障功能障碍、免疫失调和肠道微生物群失衡。尽管免疫抑制和生物治疗取得了进展，但屏障修复方面的不足和长期缓解情况表明仍需要新的治疗方法。本研究旨在确定蛋白质 - 肽复合物对预防UC中屏障破坏和结肠应激的作用。它试图回顾使用肽作为干预手段而非传统技术可能获得的作用模式、药代动力学限制和治疗益处。对分子病理生理学、临床药理学和药物递送进展的最新数据进行了文献综述和综合分析。总结了上皮再生、免疫细胞靶向和微生物群重建的机制模型。蛋白质 - 肽复合物显示出广泛的作用，包括上皮愈合、免疫抑制和微生物群控制。GLP - 2类似物和AMP偶联肽可改善紧密连接值和上皮增殖。细胞穿透肽和IL通路抑制剂联合降低促炎细胞因子（TNF - α、IL - 13、IL - 17）水平。评估了用于免疫促进、调节炎性巨噬细胞和对幼稚T细胞进行Th1偏向性免疫调节的混合免疫调节肽。肠道靶向纳米载体和pH响应系统可提高肽的生物利用度和位点特异性递送。在临床前UC模型中，肽与生物制剂的联合递送可提高临床评分。蛋白质 - 肽复合物是一类潜在的生物活性分子，可解决UC中的基本病理生理紊乱问题。它们的靶向准确性、低全身毒性和黏膜愈合潜力使其成为下一代治疗药物之一。正在进行的转化研究应结合肽工程、纳米技术和患者分层，以在UC管理中产生最大的临床影响。
