Solid-Phase Polymerization Using Anion-Exchange Resin Can Almost Completely Crosslink Hemoglobin to Prepare...

Area of Science:

• Biochemistry
• Biomaterials Science

Background:

• Hemoglobin-based oxygen carriers (HBOCs) face limitations due to unpolymerized hemoglobin, which causes vasoconstriction and hypertension.
• Current methods for removing unpolymerized hemoglobin are complex, costly, and time-consuming.

Purpose of the Study:

• To develop an efficient method for complete hemoglobin polymerization, minimizing unpolymerized hemoglobin in HBOCs.
• To evaluate the safety and efficacy of the developed polymerized hemoglobin (PolyHb) in a preclinical model.

Main Methods:

• Hemoglobin was polymerized using acetal crosslinker on anion-exchange resins (Q Sepharose Fast Flow or DEAE Sepharose Fast Flow).
• Polymerization conditions, including resin type, pH, reaction time, and molar ratios, were optimized.
• Blood pressure and blood gas parameters were monitored in mice injected with the developed PolyHb.

Main Results:

• Optimized conditions achieved almost complete hemoglobin polymerization (<1% unpolymerized hemoglobin) with a narrow molecular weight distribution.
• PolyHb produced under optimal conditions did not induce hypertension in mice.
• No pathological changes were observed in arterial oxygen, blood gas, electrolytes, or metabolic indicators.

Conclusions:

• Solid-phase polymerization using acetal is a highly effective and innovative method for producing HBOCs with minimal unpolymerized hemoglobin.
• This approach offers a promising new strategy for developing safer and more effective HBOC therapeutics.