Electrospun polymer fibers modified with FK506 for the long-term treatment of acute cardiac allograft rejection in a heart transplantation model
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...
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Published in | Biomaterials science Vol. 11; no. 11; pp. 432 - 442 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Royal Society of Chemistry
30.05.2023
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
A schematic diagram of an electrospinning device for PCL-FK506 microfibers. PCL-FK506 microfibers was applied in abdominal heterotopic heart transplantation model and its effects on survival time, immune response and secretion of cytokine. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2047-4830 2047-4849 |
DOI: | 10.1039/d3bm00374d |