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Immune Responsive Release of Tacrolimus to Overcome Organ Transplant Rejection
Author(s) -
Wu Jindao,
Zheng Zhen,
Chong Yuanyuan,
Li Xiangcheng,
Pu Liyong,
Tang Qiyun,
Yang Liu,
Wang Xuehao,
Wang Fuqiang,
Liang Gaolin
Publication year - 2018
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201805018
Subject(s) - tacrolimus , organ transplantation , transplantation , immune system , pharmacology , ciclosporin , medicine , transplant rejection , liver transplantation , immunosuppression , immunology
Transplant rejection is the key problem in organ transplantation and, in clinic, immunosuppressive agents such as tacrolimus are directly administered to the recipients after surgery for T‐cell inhibition. However, direct administration of tacrolimus may bring severe side effects to the recipients. Herein, by rational design of two hydrogelators NapPhePheGluTyrOH ( 1 ) and Nap d ‐Phe d PheGluTyrOH ( 2 ), a facile method of immune responsive release of tacrolimus is developed from their hydrogels to overcome organ transplantation rejection. Upon incubation with protein tyrosine kinase, which is activated in T cells after organ transplantation, the tacrolimus‐encapsulating Gel 1 or Gel 2 is disassembled to release tacrolimus. Cell experiments show that both Gel 1 and Gel 2 have better inhibition effect on the activated T cells than free drug tacrolimus. Liver transplantation experiments indicate that, after 7 days of treatment of same dose tacrolimus, the recipient rats in the Gel 2 group show significantly extended median survival time of 22 days while the recipients treated with conventional tacrolimus medication have a median survival time of 13 days. It is expected herein that this “smart” facile method of immune responsive release of tacrolimus can be applied to overcome organ transplantation rejection in clinic in the near future.