2. Academic Validation
  3. Target-oriented delivery of self-assembled immunosuppressant cocktails prolongs allogeneic orthotopic liver transplant survival

Target-oriented delivery of self-assembled immunosuppressant cocktails prolongs allogeneic orthotopic liver transplant survival

  • J Control Release. 2020 Dec 10;328:237-250. doi: 10.1016/j.jconrel.2020.08.043.
Haiyang Xie 1,  Hai Zhu 1,  Ke Zhou 1,  Jianqin Wan 1,  Liang Zhang 1,  Zhentao Yang 1,  Liqian Zhou 1,  Xiaona Chen 1,  Xiao Xu 1,  Shusen Zheng 2,  Hangxiang Wang 3
Affiliations

Affiliations

  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, NHC Key Laboratory of Combined Multi-Organ Transplantation; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, China.
  • 2 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, NHC Key Laboratory of Combined Multi-Organ Transplantation; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, China. Electronic address: shusenzheng@zju.edu.cn.
  • 3 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, NHC Key Laboratory of Combined Multi-Organ Transplantation; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, China. Electronic address: wanghx@zju.edu.cn.
PMID: 32866593 DOI: 10.1016/j.jconrel.2020.08.043
Abstract

Organ transplantation remains the gold standard therapeutic option for patients with end-stage organ failure. However, there have been few improvements in the management of post-transplant immunosuppression. As the long-term use of immunosuppressive agents (ISAs) may result in off-target systemic toxicity and complications, minimizing the ISA dosage while preserving the pharmacological efficacy could be a promising solution to address these challenges. Here, we present the design and application of self-assembled prodrug nanoparticles based on chemically derived mycophenolate mofetil, which further provide a hydrophobic core to noncovalently encapsulate additional ISAs such as tacrolimus. The resulting immunosuppressant cocktail nanoparticles are further refined by PEGylation with amphiphilic Polymers to form colloidally stable self-assembled immunosuppressant cocktails (SAICs) that are suitable for preclinical studies. In a rat model of allogeneic orthotopic liver transplantation (OLT), administration of SAICs markedly extends graft/recipient survival, retards weight loss and attenuates allograft damage. Furthermore, SAICs significantly abolish intragraft inflammatory cell infiltration and proinflammatory cytokine profiles as well as improve liver graft function. This study demonstrates the superiority of SAICs over traditional ISAs in the treatment of allograft rejection and may support the emerging application of the SAIC platform in clinical settings.

Keywords

Acute rejection; Immunosuppressive agent; Liver transplantation; Prodrug; Self-assembled prodrug cocktail.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z