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A novel liposomal S-propargyl-cysteine: a sustained release of hydrogen sulfide reducing myocardial fibrosis via TGF-?1/Smad pathway

Hieu Tran, Ba; Yu, Ying; Chang, Lingling; Tan, Bo; Jia, Wanwan; Xiong, Ying; Dai, Tao; Zhong, Rui; Zhang, Weiping; Minh Le, Van; Rose, Peter; Wang, Zhijun; Mao, Yicheng; Zhun Zhu, Yi

A novel liposomal S-propargyl-cysteine: a sustained release of hydrogen sulfide reducing myocardial fibrosis via TGF-?1/Smad pathway Thumbnail


Ba Hieu Tran

Ying Yu

Lingling Chang

Bo Tan

Wanwan Jia

Ying Xiong

Tao Dai

Rui Zhong

Weiping Zhang

Van Minh Le

Assistant Professor

Zhijun Wang

Yicheng Mao

Yi Zhun Zhu


Purpose: S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H2S concentrations with known cardioprotective and anti-inflammatory effects. However, its rapid metabolism and excretion have limited its clinical application. To overcome these issues, we have developed some novel liposomal carriers to deliver ZYZ-802 to cells and tissues and have characterized their physicochemical, morphological and pharmacological properties.
Methods :Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H2S concentrations. Using an in vivo model of heart failure (HF), the cardio-protective effects of liposomal carrier were determined by echocardiography, histopathology, western blot and the assessment of antioxidant and myocardial fibrosis markers.
Results: Both liposomal formulations improved ZYZ-802 pharmacokinetics and optimized H2S concentrations in plasma and tissues. Liposomal ZYZ-802 showed enhanced cardioprotective effects in vivo. Importantly, liposomal ZYZ-802 could inhibit myocardial fibrosis via the inhibition of the TGF-?1/Smad signaling pathway.
Conclusion: The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H2S within tissues.
Key word: Liposome; S-Propargyl-cysteine (SPRC, ZYZ-802); Hydrogen sulfide; Heart failure; Myocardial fibrosis; TGF-?1/Smad pathway

Journal Article Type Article
Acceptance Date Nov 15, 2019
Online Publication Date Dec 24, 2019
Publication Date 2019
Deposit Date Nov 18, 2019
Publicly Available Date Jan 9, 2020
Journal International Journal of Nanomedicine
Print ISSN 1176-9114
Electronic ISSN 1178-2013
Publisher Dove Medical Press
Peer Reviewed Peer Reviewed
Volume 2019:14
Pages 10061-10077
Public URL


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