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Nanocomplexation of thrombin with cationic amylose derivative for improved stability and hemostatic efficacy

Authors Zhuang B, Li Z, Pang J, Li W, Huang P, Wang J, Zhou Y, Lin Q, Zhou Q, Ye X, Ye H, Liu Y, Zhang LM, Chen R

Received 11 August 2014

Accepted for publication 25 October 2014

Published 29 January 2015 Volume 2015:10(1) Pages 939—947

DOI https://doi.org/10.2147/IJN.S72553

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Baoxiong Zhuang,1,* Zhihua Li,1,* Jiadong Pang,2,* Wenbin Li,1 Pinbo Huang,1 Jie Wang,1 Yu Zhou,1 Qing Lin,1 Quanbo Zhou,1 Xiao Ye,1 Huilin Ye,1 Yimin Liu,1 Li-Ming Zhang,2 Rufu Chen1

1Department of Hepato-Pancreato-Billiary Surgery, Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2DSAPM Lab and PCFM Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China

*Authors share co-first authorship


Abstract: As a topical hemostatic agent, thrombin has wide application for many surgical treatments. However, native thrombin always suffers from its physical and chemical instabilities. In this work, a nanocomplexation strategy was developed for modifying the stability and hemostatic efficacy of thrombin, in which a water-soluble cationic amylose derivative containing poly(l-lysine) dendrons was prepared by a click reaction and then used to complex thrombin in an aqueous system. For resultant thrombin nanocomplexes, their morphology and particle size distribution were investigated. Their stabilities were studied in terms of activity retention percentages under different storage time, pH values, and illumination time. In addition, their ability to achieve in vitro fibrinogen and blood coagulation were evaluated. Via a rat hepatic hemorrhage model and a rat iliac artery hemorrhage model, these thrombin nanocomplexes were confirmed to have good tissue biocompatibility and in vivo hemostatic effectiveness.

Keywords: thrombin, nanoparticles, amylose derivative, complexation, stability, hemostatic activity

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