A Novel Inflammation-Targeting Tacrolimus Hydrogel for Liver Transplantation.
1Key Laboratory of Combined Multiorgan Transplantation, Ministry of Public Health, Hangzhou, China
2Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
3Division of Biomedical Engineering and Department of Medicine, Brigham and Women's Hospital, Boston.
Meeting: 2016 American Transplant Congress
Abstract number: B44
Keywords: Adverse effects, FK506, Liver transplantation
Session Information
Session Name: Poster Session B: Allograft Rejection, Tolerance, and Xenotransplantation
Session Type: Poster Session
Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Background:Immunosuppressant have played a critical role for improving graft survival after liver transplantation (LT). While long-term systemic use of immunosuppressant such as tacrolimus (FK506) is known as an increased risk of opportunistic infections, nephrotoxicity and metabolic disorders, as well as the poor patient compliance.
Material and Methods: Our previous research has firstly developed an one-shot delivery hydrogel FK506 (FK-gel) and successfully applied in the animal lower limb transplantation. (SCIENCE TRANSLATIONAL MEDICINE 2014: 249RA110). The present research aims to investigate the application of FK-gel on LT. Orthotopicrat LT models (Loews-BN) were used to compare the effect of FK-gel injection (one bolus after liver transplantation) and oral intake (daily 0.5mg/kg). Hepatic function, immune response status and long-term survival were used in analysis. The animals was divided into 4 groups: standard liver transplantation group (OLT), OLT with hydrogel (Con-gel),hydrogel tacrolimus group (FK-gel) and tacrolimus (FK506). FK-gel group was injected with a single dose of tacrolimus (7mg/ml) after LT.
Results:There is no local skin infection, bleeding, and other systemic complications. The Short-term (14d) efficacy analysis showed: compared to OLT group, FK-gel significantly reduced tissue damage (HE), decreased AST and ALT levels, and reduced TNF-α levels. The Long-term survival analysis showed FK-gel long-term survival was significantly better than OLT group but no difference with FK506 group. The dynamic monitoring of immune status showed a significant decline of activated T cells and an increasing of Treg levels.
Conclusion: The FK-gel as the new FK506 dosage form is a safe and effective immunosuppressive agent; its short-term and long-term effects are consistent with the traditional oral administration route. The application is simple, stable and reliable, it can further increase the compliance of patients. The single dose of tacrolimus-laden hydrogel can represent one promising alternative of FK506administration in the future clinical settings.
CITATION INFORMATION: Jia J, Li J, Zhou Y, Jiang L, Zhang J, Lu H, Xie H, Zhou L, Kumur P, Zheng S. A Novel Inflammation-Targeting Tacrolimus Hydrogel for Liver Transplantation. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Jia J, Li J, Zhou Y, Jiang L, Zhang J, Lu H, Xie H, Zhou L, Kumur P, Zheng S. A Novel Inflammation-Targeting Tacrolimus Hydrogel for Liver Transplantation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/a-novel-inflammation-targeting-tacrolimus-hydrogel-for-liver-transplantation/. Accessed November 24, 2024.« Back to 2016 American Transplant Congress