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A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Synthesis, physico-chemical and biological properties of crosslinked modified hemoglobin
N P Kuznetsova1, L R Gudkin, R N Mishaeva
1Institute of Macromolecular Compounds of Russian Academy of Sciences, St. Petersburg, Russia.
Pyridoxylated hemoglobin crosslinked with glutaraldehyde forms polydisperse oligohemoglobin. This hemoglobin-based oxygen carrier demonstrates efficient oxygen transport and a half-life of 14-16 hours in vivo.
Area of Science:
- Biochemistry
- Polymer Chemistry
- Biomaterials
Background:
- Hemoglobin-based oxygen carriers (HBOCs) are investigated as blood substitutes.
- Chemical modification of hemoglobin is crucial for developing stable and effective HBOCs.
Purpose of the Study:
- To investigate the polymer aspects and reaction kinetics of pyridoxylated hemoglobin polycondensation with glutaraldehyde.
- To elucidate the mechanism of hemoglobin crosslinking into oligohemoglobin.
- To characterize the properties and in vivo behavior of the resulting oligohemoglobin.
Main Methods:
- Polycondensation reaction kinetics analysis.
- Investigation of reaction parameters (pH, component ratio, concentration).
- Electrophoretic analysis of oligohemoglobin and erythrocyte mobility.
- In vivo circulation studies in animals after intravenous infusion.
Main Results:
- A mechanism for chemical crosslinking of hemoglobin into oligohemoglobin is proposed.
- Oligohemoglobin macromolecules are polydisperse in modification degree and molecular size.
- Terminating agents influence net electric charge but not erythrocyte electrophoretic mobility.
- Oligohemoglobin solutions exhibit oxygen transport efficiency comparable to human erythrocytes.
- In vivo, low molecular weight fractions are cleared rapidly, with high molecular weight fractions accumulating in plasma.
- Oligohemoglobin exhibits a half-release period of 14-16 hours in the organism.
Conclusions:
- Glutaraldehyde-mediated polycondensation yields polydisperse oligohemoglobin with effective oxygen transport.
- Oligohemoglobin demonstrates favorable pharmacokinetic properties in vivo, with distinct clearance and accumulation patterns.
- The study provides insights into the polymerization mechanism and properties of a potential hemoglobin-based oxygen carrier.
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