Nanothin Conformal Coating with Poly(N-vinylpyrrolidone) and Tannic Acid (PVPON/TA) Preserves Murine and Human Pancreatic Islets Function

• Published in: Pharmaceutics Vol. 15; no. 4; p. 1137
• Main Authors: Polishevska, Kateryna, Kelly, Sandra, Kuppan, Purushothaman, Seeberger, Karen L, Aggarwal, Saloni, Paramor, Joy, Unsworth, Larry D, Tse, Hubert M, Korbutt, Gregory S, Pepper, Andrew R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04-04-2023; MDPI
• Subjects: allotransplantation; conformal coating; Diabetes; encapsulation; Glucose; human islets; Hypoglycemia; Insulin; islet transplantation; Laboratories; Physiology; Scanning electron microscopy; Transplants & implants; type 1 diabetes; Canada; United States > US; encapsulation; type 1 diabetes; islet transplantation; human islets; allotransplantation; conformal coating
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15041137

Beta cell replacement therapies can restore glycemic control to select individuals living with type 1 diabetes. However, the obligation of lifelong immunosuppression restricts cell therapies from replacing exogenous insulin administration. Encapsulation strategies can reduce the inherent adaptive immune response; however, few are successfully translated into clinical testing. Herein, we evaluated if the conformal coating of islets with poly(N-vinylpyrrolidone) (PVPON) and tannic acid (TA) (PVPON/TA) could preserve murine and human islet function while conferring islet allograft protection. In vitro function was evaluated using static glucose-stimulated insulin secretion, oxygen consumption rates, and islet membrane integrity. In vivo function was evaluated by transplanting human islets into diabetic immunodeficient B6.129S7-Rag
/J (Rag
) mice. The immunoprotective capacity of the PVPON/TA-coating was assessed by transplanting BALB/c islets into diabetic C57BL/6 mice. Graft function was evaluated by non-fasting blood glucose measurements and glucose tolerance testing. Both coated and non-coated murine and human islets exhibited indistinguishable in vitro potency. PVPON/TA-coated and control human islets were able to restore euglycemia post-transplant. The PVPON/TA-coating as monotherapy and adjuvant to systemic immunosuppression reduced intragraft inflammation and delayed murine allograft rejection. This study demonstrates that PVPON/TA-coated islets may be clinically relevant as they retain their in vitro and in vivo function while modulating post-transplant immune responses.