Development of low molecular weight heparin by H2O2/ascorbic acid with ultrasonic power and its anti-metastasis property

Xuemin Shen, Zhenfeng Liu, Junhui Li, Dongmei Wu, Meng Zhu, Lufeng Yan, Guizhu Mao, Xingqian Ye, Robert J. Linhardt, Shiguo Chen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Low molecular weight heparins (LMWHs) are currently used as an anticoagulant agent since unfractionated heparin (UFH) can cause serious adverse drug reactions. LMWHs are commercially prepared using different methods such as nitrous acid cleavage and β-elimination under strong reaction conditions or with harsh chemicals, which may cause the saccharide units within the polysaccharide backbone to be decomposed and noticeably modified. This study demonstrates an effective method for depolymerizing heparin via the production of large amounts of free radicals from H2O2/ascorbic acid and ultrasonic power; this results in highly pure products because ascorbic acid can decompose during the reaction, which is different from the previously reported H2O2/Cu2+ method. The reaction conditions—including concentration of ascorbic acid, reaction temperature and intensity of ultrasonic power—were investigated and optimized. We found that the degradation behavior of heparin in this combined physicochemical process conformed to first-order reaction kinetics. The chemical composition and structures of different LMWHs were analyzed. The results showed the primary structure and sulfate esters were well preserved after the depolymerization, the major repeat units are (1–4)-linked glucosamine and iduronic acid. The further in vitro assays indicated that the LMWHs produced by H2O2/ascorbic acid with ultrasonic power have an anti-metastatic effect in A549 cells, which suggested the LMWHs rapidly prepared in this physicochemical way have a potential for anti-tumor metastatic function.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalInternational Journal of Biological Macromolecules
Volume133
DOIs
StatePublished - 15 Jul 2019
Externally publishedYes

Keywords

  • Anti-metastasis
  • Low molecular weight heparin
  • Radical reaction
  • Ultrasonic degradation

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