Synthesis and Study of Hypoxia-Responsive Micelles Based on Hyaluronic Acid

doi:10.6023/A17070336

Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (1): 35-42.DOI: 10.6023/A17070336 Previous Articles Next Articles

Article

基于透明质酸的缺氧响应型胶束的制备及性能研究

张蓓^a, 常柏松^b, 孙涛垒^a,b

a 武汉理工大学化学化工与生命科学学院武汉 430070;
b 武汉理工大学材料复合新技术国家重点实验室武汉 430070

投稿日期:2017-07-25 发布日期:2017-11-10
通讯作者: 孙涛垒 E-mail:suntl@whut.edu.cn
基金资助:
项目受国家杰出青年基金（No.51325302）、国家自然科学基金（No.51533007）、国家重点基础研究发展规划项目（No.2013CB933002）、复旦大学聚合物分子工程国家重点实验室开放项目（No.K2017-10）和湖北省自然科学基金（No.2015CFB304）资助.

Synthesis and Study of Hypoxia-Responsive Micelles Based on Hyaluronic Acid

Zhang Bei^a, Chang Baisong^b, Sun Taolei^a,b

a School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070;
b State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070

Received:2017-07-25 Published:2017-11-10
Contact: 10.6023/A17070336 E-mail:suntl@whut.edu.cn
Supported by:
Project supported by the China National Funds for Distinguished Young Scientists (No. 51325302), the National Natural Science Foundation of China (No. 51533007), the Major State Basic Research Development Program of China (No. 2013CB933002), the Open Project Program of the State Key Lab of Molecular Engineering of Polymers, the Fudan University (No. K2017-10) and the Natural Science Foundation of Hubei Province (No. 2015CFB304).

1. Synthesis and Study of Hypoxia-Responsive Micelles Based on Hyaluronic Acid.PDF(504KB)

Abstract

Hypoxia is a hallmark of tumor. Based on this feature, a hypoxia-responsive drug delivery system combined with tumor-targeting was developed. HA-NI conjugates were prepared by grafting the carboxyl group of hyaluronic acid (HA) with an amine group of nitroimidazole (NI) derivative in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The structure of HA-NI conjugates was confirmed by FT-IR and ¹H NMR, the degree of substitution (DS) of NI derivative was also calculated based on ¹H NMR. Amphiphilic HA-NI conjugates could self-assemble into micelles by ultrasonic method. The size and morphology of micelles were characterized by dynamic light scattering (DLS), atomic force microscope (AFM) and transmission electron microscopy (TEM), the stability of micelles was also investigated by DLS. It was found the size of micelles was in the range of 80~220 nm while the DS decreased from 6.5% to 3.6%. Doxorubicin (DOX) was encapsulated in micelles, and DOX-loaded micelles had smaller sizes compared with blank micelles. Drug-loading (DL) and entrapment efficiency (EE) were obtained by UV-Vis analysis and increased with the increasing DS. Under hypoxic condition, micelles became bigger and size distribution of micelles became wider, it was clear to observe the destruction of micelles by AFM and TEM. UV spectrum revealed the characteristic peak belonging to NI at 325 nm disappeared and Zeta potential increased from -30.6±0.4 mV to -24.9±0.5 mV 6 h later. In vitro drug release studies demonstrated that DOX was released from HA-NI micelles in a hypoxia-dependent manner:micelles were sufficiently stable at normoxic condition while accomplished a rapid drug release under hypoxic condition.

Key words: drug delivery system, hypoxia-responsive, hyaluronic acid, nitroimidazole, micelles

Cite this article

Zhang Bei, Chang Baisong, Sun Taolei. Synthesis and Study of Hypoxia-Responsive Micelles Based on Hyaluronic Acid[J]. Acta Chim. Sinica, 2018, 76(1): 35-42.

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基于透明质酸的缺氧响应型胶束的制备及性能研究

Synthesis and Study of Hypoxia-Responsive Micelles Based on Hyaluronic Acid

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