Conjugated Human Hemoglobin as a Physiological Oxygen Carrier - Pyridoxalated Hemoglobin Polyoxyethylene Conjugate (PHP)

Abstract

Problems associated with specific physiological properties of Hb-based blood substitutes, such as low P50, short plasma half-life and nephrotoxicity are still major issues to be addressed. Extensive investigations aimed at overcoming these problems have resulted in the preparation of pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP). PHP was developed from human hemoglobin by two major chemical modifications; pyridoxylation for the purpose of lowering the oxygen affinity (P50 of 19.5 +/- 1.2 mmHg), and coupling with polyoxyethylene (POE) to increase its molecular weight (to approximately 90 kdaltons). The circulating half-life of PHP is about 40 hours in dogs. Toxicological and physiological studies including renal function assessments have demonstrated that PHP does not have untoward effects on major organ functions. Its efficacy in transporting oxygen has been shown in ET and intracoronary perfusion, and in in vitro studies with sickle cells. Studies to date suggest that PHP is a promising candidate as a physiological oxygen carrier. In this paper the properties of PHP, its safety and efficacy aspects, and its potential as a clinical oxygen carrier are reviewed based on studies conducted in the Author's laboratory.