Nanofiber-Mediated Sustained Delivery of Triiodothyronine: Role in Angiogenesis

Abstract

Angiogenesis is a vital component of the orchestrated wound healing cascade and tissue regeneration process, which has a therapeutic prominence in treatment of ischemic vascular diseases and certain cardiac conditions. Based on its eminence, several strategies using growth factors have been studied to initiate angiogenesis. However, growth factors are expensive and have short half-life. In this work, sustained release of triiodothyronine, which plays a crucial role in stimulating growth factors and other signaling pathways that are instrumental in initiating angiogenesis, has been attempted through electrospun polycaprolactone nanofibers. This delivery system enabled the slow and sustained delivery of triiodothyronine into the micro-environment, reducing seepage of excess into systemic circulation and eliminating the necessity of repeated dosage forms. It was observed that triiodothyronine-incorporated nanofibers exhibited favorable interaction with cells (phalloidin staining of actin filaments) and also enhanced the rate of endothelial proliferation, migration, and adhesion. The angiogenic potential of these nanofibers was further corroborated through chorioallantoic membrane and rat aortic ring assay (demonstrating cell sprouting area of 3.3 ± 0.71 mm2 compared to 1.2 ± 0.01 mm2 in control). The nanofiber matrix thus fabricated demonstrated a vibrant therapeutic potential to induce angiogenesis. Triiodothyronine also plays a significant role in wound healing independent of initiating angiogenesis. This further substantiates the positive impact of this delivery system as a dressing material for chronic wound therapeutics, ischemic vascular diseases, and certain cardiac conditions.

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Acknowledgements

The authors are grateful to the Director, CSIR – CLRI for his constant support. The research is carried out as a part of Ph.D. work registered in the University of Madras, Chennai. The first author would like to acknowledge the DST-INSPIRE programme, New Delhi for the research fellowship (IF130876).

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Correspondence to Purna Sai Korrapati.

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Satish, A., Korrapati, P.S. Nanofiber-Mediated Sustained Delivery of Triiodothyronine: Role in Angiogenesis. AAPS PharmSciTech 20, 110 (2019). https://doi.org/10.1208/s12249-019-1326-y

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Key Words

  • triiodothyronine
  • angiogenesis
  • nanofibers
  • polycaprolactone
  • wound healing