Liposome/Heme as a Totally Synthetic Oxygen Carrier

Abstract

We synthetically derived protoheme (oxygen-binding site of hemoglobin) to an amphiphilic heme compound and embedded it in the phospholipid bilayer of liposomes, not in an aqueous inside region of liposomes. This liposome/heme transports oxygen efficiently under physiological conditions. Characteristics of our totally synthetic liposome/heme as an artificial oxygen carrier, are summarized as follows, (i) Oxygen-binding is reversible and very rapid, (ii) The oxygen volume dissolved in the fluid is similar or superior to that of blood, (iii) The oxygen-binding affinity is close to that of blood, (iv) The particle size is smaller than 0.1 u m. (v) It is physically and mechanically stable under shear stress and storage. (vi) The components are synthetic derivatives of protoheme and phospholipid originated in nature. The advantages (i)-(iii) and brilliant red color of the solution are derived from the fact that our totally synthetic liposome/heme, transports oxygen in the same principle of red blood cells. When the liposome/heme solution was mixed with human blood, the liposome/heme delivered oxygen to blood in the mixture system. The oxygen-exchanging of the liposome/heme with blood was also tested ex-vivo using an artificial lung apparatus. The oxy liposome/heme was circulated through A-V of a dog leg, and the oxygen concentration was kept at a high level. This demonstrates the fact that the synthetic liposome/heme transports and delivers oxygen to the muscle tissue. Application to extracorporeal circulation and transfusion test will also be reported.