Immune Responsive Release of Tacrolimus to Overcome Organ Transplant Rejection

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....

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Bibliographic Details
Published in:Advanced materials (Weinheim) 2018-11, Vol.30 (45), p.e1805018-n/a
Main Authors: Wu, Jindao, Zheng, Zhen, Chong, Yuanyuan, Li, Xiangcheng, Pu, Liyong, Tang, Qiyun, Yang, Liu, Wang, Xuehao, Wang, Fuqiang, Liang, Gaolin
Format: Article
Language:English
Subjects:
Animals
Dismantling
Drug Delivery Systems - methods
Graft Rejection - drug therapy
Graft Rejection - immunology
Humans
Hydrogels
Hydrogels - chemical synthesis
Hydrogels - chemistry
Hydrophobic and Hydrophilic Interactions
immune responsive release
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - blood
Liver
Liver Transplantation
Lymphocytes
Materials science
Models, Animal
organ transplant rejection
protein tyrosine kinase
Protein-Tyrosine Kinases - metabolism
Proteins
Rats
Rejection
Side effects
Survival
T-Lymphocytes - enzymology
tacrolimus
Tacrolimus - administration & dosage
Tacrolimus - blood
Transplantation
Transplants & implants
Tyrosine
Viscoelastic Substances - chemical synthesis
Viscoelastic Substances - chemistry
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Summary: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 NapPhePheGluTyrOH (1) and Nap d‐Phe dPheGluTyrOH (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. Upon phosphorylation by the protein tyrosine kinase from activated T cells after organ transplantation, hydrogelators in the tacrolimus‐coassembled nanofibers will be efficiently converted to their hydrophilic phosphates, resulting in the disassembly of the nanofibers and the release of tacrolimus for T‐cell inhibition.
ISSN:0935-9648
1521-4095
DOI:10.1002/adma.201805018