Taguchi Kazuaki, Yamasaki Keishi, Maruyama Toru, Otagiri Masaki
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 862-0082, Japan.
DDS Research Institute, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 862-0082, Japan.
J Funct Biomater. 2017 Mar 18;8(1):11. doi: 10.3390/jfb8010011.
Hemoglobin (Hb) is an ideal material for use in the development of an oxygen carrier in view of its innate biological properties. However, the vascular retention of free Hb is too short to permit a full therapeutic effect because Hb is rapidly cleared from the kidney via glomerular filtration or from the liver via the haptogloblin-CD 163 pathway when free Hb is administered in the blood circulation. Attempts have been made to develop alternate acellular and cellular types of Hb based oxygen carriers (HBOCs), in which Hb is processed via various routes in order to regulate its pharmacokinetic properties. These HBOCs have been demonstrated to have superior pharmacokinetic properties including a longer half-life than the Hb molecule in preclinical and clinical trials. The present review summarizes and compares the pharmacokinetic properties of acellular and cellular type HBOCs that have been developed through different approaches, such as polymerization, PEGylation, cross-linking, and encapsulation.
鉴于血红蛋白(Hb)固有的生物学特性,它是开发氧载体的理想材料。然而,游离Hb在血管内的留存时间过短,无法产生充分的治疗效果,因为当游离Hb在血液循环中给药时,它会通过肾小球滤过迅速从肾脏清除,或通过触珠蛋白-CD163途径从肝脏清除。人们已尝试开发基于Hb的替代无细胞和细胞类型的氧载体(HBOC),其中Hb通过各种途径进行处理,以调节其药代动力学特性。在临床前和临床试验中,这些HBOC已被证明具有优异的药代动力学特性,包括比Hb分子更长的半衰期。本综述总结并比较了通过不同方法(如聚合、聚乙二醇化、交联和封装)开发的无细胞和细胞类型HBOC的药代动力学特性。