2. Academic Validation
  3. Electrospun polymer fibers modified with FK506 for the long-term treatment of acute cardiac allograft rejection in a heart transplantation model

Electrospun polymer fibers modified with FK506 for the long-term treatment of acute cardiac allograft rejection in a heart transplantation model

  • Biomater Sci. 2023 May 2. doi: 10.1039/d3bm00374d.
Cheng Deng 1 2 3,  Qiaofeng Jin 1 2 3,  Jia Xu 1 2 3,  Wenpei Fu 1 2 3,  Mengrong He 1 2 3,  Lingling Xu 1 2 3,  Yishu Song 1 2 3,  Wenyuan Wang 1 2 3,  Luyang Yi 1 2 3,  Yihan Chen 1 2 3,  Tang Gao 1 2 3,  Jing Wang 1 2 3,  Qing Lv 1 2 3,  Yali Yang 1 2 3,  Li Zhang 1 2 3,  Mingxing Xie 1 2 3
Affiliations

Affiliations

  • 1 Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. zli429@hust.edu.cn.
  • 2 Hubei Province Clinical Research Center for Medical Imaging, Wuhan, 430022, China.
  • 3 Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
PMID: 37129635 DOI: 10.1039/d3bm00374d
Abstract

FK506, a first-line immunosuppressant, is routinely administered orally and intravenously following heart transplantation. However, frequent administration can result in a substantial psychological burden to patients, resulting in non-adherence to medication. The purpose of our study is to overcome the disadvantages of systemic drug administration by developing a polymer-based delivery system that is tunable and biodegradable and that can release highly hydrophobic FK506 over extended periods to treat or prevent acute cardiac allograft rejection. Using an electrospinning method, long-acting microfibers were prepared, and FK506 appeared to be continuously released for up to 14 days based on the in vitro release profiles. After implanting the microfiber subcutaneously into the abdominals of transplanted rats, it was found that the infiltration of T cells and macrophages and the secretion of interleukin-2 (IL-2) and IL-1β were significantly reduced compared with those of the free FK506 groups. More importantly, the mean survival time (MST) of the PCL-FK506 group was significantly extended in comparison with that of untreated control recipients and free FK506 (MST of untreated control recipients, free FK506, and PCL-FK506 was 8, 26.1, and 37, respectively). In conclusion, we propose that this drug delivery approach would be suitable for developing long-lasting immunomodulatory agents that prolong cardiac graft survival safely and effectively.

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