Fibroblast growth factor 21 (FGF21) shows great therapeutic potential in metabolic, neurodegenerative and inflammatory diseases. However, current FGF21 administration predominantly relies on injection rather than oral ingestion due to its limited stability and activity post-gastrointestinal transit, thereby hindering its clinical utility. Milk-derived exosomes (mEx) have emerged as a promising vehicle for oral drug delivery due to their ability to maintain structural integrity in the gastrointestinal milieu. To address the challenge associated with oral delivery of FGF21, we encapsulated FGF21 within mEx (mEx@FGF21) to protect its activity post-oral administration. Additionally, we modified the surface of mEx@FGF21 by introducing transferrin (TF) to enhance intestinal absorption and transport, designated TF-mEx@FGF21. results demonstrated that the surface modification of TF promoted FGF21 internalization by intestinal epithelial cells. Orally administered TF-mEx@FGF21 showed promising therapeutic effects in septic mice. This study represents a practicable strategy for advancing the clinical application of oral FGF21 delivery.

中文翻译：

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口服 FGF21 减轻脓毒症炎症和多器官损伤的策略

成纤维细胞生长因子 21 (FGF21) 在代谢、神经退行性疾病和炎症性疾病方面显示出巨大的治疗潜力。然而，目前的FGF21给药主要依靠注射而不是口服摄入，因为其在胃肠道转运后的稳定性和活性有限，从而阻碍了其临床应用。乳源性外泌体（mEx）因其能够在胃肠道环境中保持结构完整性而成为一种有前途的口服药物递送载体。为了解决与 FGF21 口服给药相关的挑战，我们将 FGF21 封装在 mEx (mEx@FGF21) 中，以保护其口服后的活性。此外，我们通过引入转铁蛋白（TF）对mEx@FGF21的表面进行修饰，以增强肠道吸收和转运，命名为TF-mEx@FGF21。结果表明，TF的表面修饰促进了肠上皮细胞对FGF21的内化。口服 TF-mEx@FGF21 对脓毒症小鼠显示出有希望的治疗效果。这项研究代表了推进口服 FGF21 递送临床应用的可行策略。