Effects of subcutaneous vs. oral nanoparticle-mediated insulin delivery on hemostasis disorders in type 1 diabetes: A rat model study

Nawel Kaddour, Farah Benyettou, Kawtar Moulai, Abdelouahab Mebarki, Katia Allal-Taouli, Rose Ghemrawi, Jamie Whelan, Hafida Merzouk, Ali Trabolsi, Nassima Amel Mokhtari-Soulimane

Research output: Contribution to journalArticlepeer-review


Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.

Original languageEnglish (US)
Article numbere30450
Issue number9
StatePublished - May 15 2024


  • Covalent organic framework nanoparticles (nCOF)
  • Diabetes complications
  • Hemostasis disorders
  • Insulin delivery
  • Type 1 diabetes

ASJC Scopus subject areas

  • General


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