2. Academic Validation
  3. A strategy for oral delivery of FGF21 for mitigating inflammation and multi-organ damage in sepsis

A strategy for oral delivery of FGF21 for mitigating inflammation and multi-organ damage in sepsis

  • Int J Pharm. 2024 May 10:656:124115. doi: 10.1016/j.ijpharm.2024.124115.
Xinze Li 1,  Dedong Yu 2,  Xuanhe Chen 2,  Zhiwei Huang 3,  Yingzheng Zhao 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China.
  • 2 Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
  • 3 Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: hzwpharm@163.com.
  • 4 Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo 315300, China. Electronic address: pharmtds@163.com.
PMID: 38614430 DOI: 10.1016/j.ijpharm.2024.124115
Abstract

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. In vitro 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.

Keywords

Fibroblast growth factor 21; Milk-derived exosomes; Oral administration; Sepsis.

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