Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with I-125 (I-125-HbV) and cell-free I-125-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using I-125-HbV and H-3-HbV (liposomal cholesterol was radiolabeled with tritium-3). The time courses for the plasma concentration curves of I-125-HbV, H-3-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. I-125-HbV and H-3-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.

血红蛋白囊泡（HbV）是一种人造氧载体，它将浓缩的血红蛋白溶液包裹在脂质囊泡（脂质体）中。在小鼠和大鼠中对HbV的药代动力学特性进行了研究。使用内部血红蛋白用I - 125标记的HbV（I - 125 - HbV）以及无细胞的I - 125 - Hb，发现血红蛋白的包裹使其半衰期延长了30倍，同时肝脏和肾脏中的分布减少。HbV的半衰期增加，并且随着HbV剂量的增加，肝脏和脾脏的摄取清除率降低。在一项体外研究中，发现RAW 264.7细胞对HbV有特异性摄取和降解，但实质细胞和内皮细胞并非如此。还使用I - 125 - HbV和H - 3 - HbV（脂质体胆固醇用氚 - 3进行放射性标记）对HbV成分（内部血红蛋白和脂质体脂质）的药代动力学进行了研究。I - 125 - HbV、H - 3 - HbV以及来自HbV的铁的血浆浓度曲线的时间进程表明，HbV在注射后长达24小时在血液循环中保持完整结构。I - 125 - HbV和H - 3 - HbV主要分布在肝脏和脾脏。注射5天后，内部血红蛋白从肝脏和脾脏中消失，脂质体胆固醇在大约14天后消失。内部血红蛋白通过尿液排泄，胆固醇通过胆汁排泄进入粪便。这些结果表明HbV具有合理的血液滞留以及代谢和排泄性能，可作为一种氧载体。