Polyethylene glycol-modified liposome-encapsulated hemoglobin: a long circulating red cell substitute.
Polyethylene glycol-modified liposome-encapsulated hemoglobin: a long circulating red cell substitute.
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发表时间：
1999-02
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通讯作者：
W. Phillips;R. Klipper;V. Awasthi;A. Rudolph;R. Cliff;V. Kwasiborski;B. Goins
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作者：
W. Phillips;R. Klipper;V. Awasthi;A. Rudolph;R. Cliff;V. Kwasiborski;B. Goins
红细胞替代品发展的一个主要障碍是克服其短循环持久性。在这项研究中，二硬脂酰磷酸乙醇胺聚乙二醇5000（PEG-PE）（10摩尔%）加入到脂质体包裹的血红蛋白（莱赫）的配方，以减少网状内皮系统的摄取和延长莱赫循环持久性。用锝-99 m对PEG-LEH进行放射性标记，输注到兔子体内（以1 ml/min的速度占血池的25%）（n = 5），并在48小时内的不同时间通过闪烁成像进行监测。在48 h时，处死动物，并收集组织样品用于在闪烁孔计数器中计数。48 h时的组织分布数据显示，51.3 +/- 3.4%的锝-99 m-PEG-莱赫保留在循环中，与先前报道的不含PEG的莱赫制剂的循环半衰期相比，循环半衰期增加了3倍以上。肝脏在48 h时的蓄积最大（12.7 +/- 0.7%），其次是骨髓（6.2 +/- 0.1%），而脾脏仅为1.4 +/-0.2%。将PEG-PE添加到莱赫制剂中极大地提高了莱赫的循环持久性，并且代表了在开发具有延长的氧输送的红细胞替代品方面的重要步骤。
A major obstacle in the development of red cell substitutes has been overcoming their short circulation persistence. In this study, distearoyl phosphoethanolamine polyethylene glycol 5000 (PEG-PE) (10 mol%) was added to the formulation of liposome-encapsulated hemoglobin (LEH) to decrease reticuloendothelial system uptake and prolong LEH circulation persistence. PEG-LEH was radiolabeled with technetium-99m, infused into rabbits (25% of blood pool at 1 ml/min) (n = 5), and monitored by scintigraphic imaging at various times out to 48 h. At 48 h, animals were sacrificed, and tissue samples were collected for counting in a scintillation well counter. Tissue distribution data at 48 h revealed that 51.3 +/- 3.4% of the technetium-99m-PEG-LEH remained in circulation, a greater than 3-fold increase in the circulation half-life compared with circulation half-lives previously reported for non-PEG-containing LEH formulations. The liver had the greatest accumulation at 48 h (12.7 +/- 0.7%), followed by bone marrow (6.2 +/- 0.1%), whereas the spleen had only 1.4 +/- 0.2%. The addition of PEG-PE to the LEH formulation greatly prolongs the circulation persistence of LEH and represents a significant step in the development of red cell substitutes with prolonged oxygen delivery.