Pharmacokinetic properties of hemoglobin vesicles as a substitute for red blood cells

Abstract

The development of artificial oxygen carriers has attracted considerable recent interest because of the increasing cost of collecting and processing blood, public concerns about the safety of blood products, complications from blood transfusions, military requirements for increased volumes of blood during military conflicts, and a decrease in the number of new donors. To overcome these problems, perfluorocarbon-based oxygen carriers as well as acellular- and cellular-type, hemoglobin-based oxygen carriers have been developed for use as artificial oxygen carriers. Despite their extensive evaluation, including formulation and pharmacology, they have not been extensively used in clinical settings. One of the reasons for this is that their pharmacokinetics have not been well characterized. Artificial oxygen carriers require not only an acceptable level of physicochemical activity, but also clinical efficacy, as reflected by their retention in the circulation, and the absence of measurable accumulation in the body, if unexpected adverse effects are to be avoided. In this review, the pharmacokinetic properties of artificial oxygen carriers are discussed, with a focus on recent developments of our research related to the pharmacokinetic properties a cellular type of hemoglobin-based oxygen carrier.

Keywords::

• Artificial oxygen carrier
• disposition
• liposome
• mononuclear phagocyte system
• hemorrhagic shock
• hepatic chronic cirrhosis
• accelerated blood clearance phenomenon

Acknowledgments

The authors acknowledge Emeritus Prof. Eishun Tsuchida, Dr. Hiromi Sakai (Waseda University), Prof. Koichi Kobayashi, Dr. Hirohisa Horinouchi (Keio University), Prof. Shokei Kim-Mitsuyama, Dr. Eiichiro Yamamoto, Dr. Hiroshi Watanabe, Dr. Daisuke Kadowaki, Ms. Yukino Urata, Ms. Mayumi Miyasato (Kumamoto University), Dr. Toshiya Kai (Nipro Corp., Osaka, Japan), Dr. Makoto Anraku (Fukuyama University), Dr. Yasunori Iwao (University of Shizuoka), and their active colleagues for meaningful discussion and contributions to this research.

Declaration of interest

The authors declare no financial conflicts of interest. The authors alone are responsible for the content and writing of this paper.