4.8 Article

Prolongation of graft survival via layer-by-layer assembly of collagen and immunosuppressive particles on pancreatic islets

Journal

BIOMATERIALS
Volume 290, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121804

Keywords

Islet transplantation; Layer-by-layer coating; Conformal coating; Tacrolimus; Local drug delivery

Funding

  1. National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2021K1A3A1A20002609]
  2. Bio & Medical Technology Development Program of the NRF - Korean government (MSIT) [2022M3A9G8017220]
  3. Korean Fund for Regenerative Medicine - Ministry of Science and ICT
  4. Ministry of Health Welfare [22A0205L1]
  5. National Research Foundation of Korea [2021K1A3A1A20002609, 2022M3A9G8017220] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study presents a strategy for site-specific delivery of an immunosuppressant using layer-by-layer assembly of polymeric particles and collagen on pancreatic islets. The controlled release of the drug achieved therapeutic effects in a rodent model of type 1 diabetes, offering potential for improved outcomes and safety in cell therapies for curing the disease.
Pancreatic islet transplantation holds great potential as a curative therapy for treating type 1 diabetes. However, the need for lifelong systemic immunosuppression with inevitable side effects is an obstacle to clinical success. Here we devised a strategy for the site-specific delivery of an immunosuppressant (tacrolimus) using layer-by-layer assembly of polymeric particles and collagen on the islet surface. This approach aims to provide a continuous and sustained supply of tacrolimus in the vicinity of transplanted cells while avoiding systemic drug exposure. The dose and release rate of tacrolimus can be tunable to achieve therapeutic windows by varying layer-by-layer construction and chemistry of polymers. Transplanting 400 IEQ of pancreatic islets coated with particles containing similar to 3 mu g of TAC per recipient provided controlled drug release and rectified diabetes for up to 5 months in a xenogeneic rodent model of type 1 diabetes. We anticipate that the findings of this study will be found useful by those developing local immunomodulation strategies aimed at improving the outcomes and safety of cell therapies for curing type 1 diabetes.

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