Pilot scale production and characterization of next generation high molecular weight and tense quaternary state polymerized human hemoglobin
Abstract
Polymerized human hemoglobin (PolyhHb) is being studied as a possible red blood cell (RBC) substitute for use in scenarios where blood is not available. While the oxygen (O2) carrying capacity of PolyhHb makes it appealing as an O2 therapeutic, the commercial PolyhHb PolyHeme® (Northfield Laboratories Inc.) was never approved for clinical use due to the presence of large quantities of low molecular weight (LMW) polymeric hemoglobin (Hb) species (0.2 µm and <500 kDa) in the material, to create a product that should be safer for transfusion. Therefore, to enable future large animal studies and eventual human clinical trials, PolyhHb synthesis and purification processes need to be scaled up to the pilot scale. Hence in this study, we describe the pilot scale synthesis and purification of PolyhHb. Characterization of pilot scale PolyhHb showed that PolyhHb could be successfully produced to yield biophysical properties conducive for its use as an RBC substitute. Size exclusion high performance liquid chromatography showed that pilot scale PolyhHb yielded a high molecular weight Hb polymer containing a small percentage of LMW Hb species (<500 kDa). Additionally, the auto‐oxidation rate of pilot scale PolyhHb was even lower than that of previous generations of PolyhHb. Taken together, these results demonstrate that PolyhHb has the ability to be seamlessly manufactured at the pilot scale to enable future large animal studies and clinical trials.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 03, 2022
- Source ID
- 10.1002/bit.28233
Entities
People
- Alisyn Greenfield
- Andre F. Palmer
- Clayton Cuddington
- Donald A Belcher
- Megan Allyn
- Richard Hickey
- Savannah R. Wolfe
- Shuwei Lu
- Tanmay Salvi
- Xiangming Gu
Organizations
- Ohio State University
- United States Department of Defense