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A purification process for heparin and precursor polysaccharides using the pH responsive behavior of chitosan
Ujjwal Bhaskar1, Anne M Hickey1, Guoyun Li1
1Dept. of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY.
Biotechnology Progress
|July 7, 2015
Summary
A novel chitosan-based purification method simplifies the production of bioengineered heparin, addressing safety concerns from animal-derived sources. This cost-effective approach ensures high-purity heparin suitable for pharmaceutical applications.
Area of Science:
- Biotechnology
- Biochemistry
- Chemical Engineering
Background:
- Heparin contamination crises highlight risks of animal-derived heparin.
- Chemical synthesis of heparin is not feasible.
- Bioengineered heparin offers a safer alternative, but requires efficient production processes.
Purpose of the Study:
- To develop a cost-effective chitosan-based purification process for bioengineered heparin.
- To improve the safety and purity of heparin for pharmaceutical use.
- To address challenges in large-scale bioengineered heparin production.
Main Methods:
- Utilized 96-well plate screening for process development.
- Employed chitosan's pH-responsive properties for selective capture and elution of heparin and precursor polysaccharides.
- Applied selective precipitation of glycosaminoglycans (GAGs) to remove impurities.
- Analyzed product composition using liquid chromatography-mass spectrometry and nuclear magnetic resonance.
Main Results:
- Chitosan enables simplified capture and elution of target polysaccharides under specific pH conditions.
- Mild basic elution conditions are compatible with subsequent N-deacetylation/N-sulfonation steps.
- Selective precipitation effectively removed proteins, DNA, and endotoxins.
- Chitosan purification demonstrated minimal impact on the final heparin product composition.
Conclusions:
- A chitosan-based purification process is effective for producing high-purity bioengineered heparin.
- This method offers a viable, cost-competitive alternative to animal-derived heparin.
- The process is compatible with existing bioengineering strategies for heparin production.
