Artificial Oxygen Carriers: Lessons From Hemoglobin-Based Oxygen Carrier Clinical Trials and Current Development...

Area of Science:

• Biomedical Engineering
• Hematology
• Toxicology

Background:

• Donated blood transfusions have limitations including supply shortages, short shelf-life, and infectious disease transmission risks.
• Cell-free hemoglobin-based oxygen carriers (HBOCs) have been explored as alternatives to red blood cell transfusions for decades.
• Early HBOCs faced safety issues like hypertension and organ toxicity due to hemoglobin's reactive heme center.

Purpose of the Study:

• To review the historical development of HBOCs.
• To analyze the reasons for the failure of previous HBOC programs.
• To discuss the current status of artificial oxygen carrier development.

Main Methods:

• Literature review of HBOC development and clinical trials.
• Analysis of safety data and adverse events from preclinical and clinical studies.
• Examination of strategies employed to modify hemoglobin for improved safety and efficacy.

Main Results:

• Despite modifications, HBOCs have consistently shown elevated adverse events in large clinical trials.
• No HBOC has successfully met clinical endpoints or received US FDA approval.
• The reactive nature of hemoglobin's heme center remains a significant challenge.

Conclusions:

• Significant hurdles remain in developing safe and effective HBOCs.
• Lessons learned from past failures are crucial for future artificial oxygen carrier development.
• Ongoing research focuses on overcoming the inherent toxicities of hemoglobin-based oxygen carriers.