Updike S J, Wakamiya R T
J Lab Clin Med. 1983 May;101(5):679-91.
In order to evaluate enzyme loading of RBCs as a drug delivery system, the antitumor agent asparaginase was loaded into the erythrocytes of nine monkeys at three different doses and autologously injected back into these animals. Nine control monkeys were also once injected intravenously at the same doses of enzyme, but the enzyme was free in solution rather than entrapped in RBCs. The RBCs and asparaginase were labeled with 51Cr and 125I, respectively. The circulating half-life of the enzyme-loaded, resealed RBCs was 7 days, as compared to 9 days in the control RBCs. Beginning at 5 days, circulating enzyme activity was several orders of magnitude higher in the monkeys injected with RBC-loaded asparaginase than in controls. Targeting of drug-loaded RBCs into the spleen and liver was apparent. Suppression of the serum substrate level of asparaginase in the monkeys treated with the single intravenous injection of RBCs loaded with asparaginase was 20 days, which was twice as long as the suppression in the control monkeys. Production of anti-asparaginase antibody was shown to reach a higher level and persist longer in the monkeys with RBC-entrapped asparaginase. Evidence was also obtained showing that entrapping asparaginase in RBCs protects against anaphylaxis in the guinea pig. Thus this drug delivery system is also proposed as a strategy to avoid life-threatening allergic reactions. Advantages and limitations of RBC loading as a drug delivery system are discussed.
为了评估红细胞作为药物递送系统的酶负载情况，将抗肿瘤药物天冬酰胺酶以三种不同剂量负载到九只猴子的红细胞中，并将其自体回注到这些动物体内。另外九只对照猴子也以相同的酶剂量进行了一次静脉注射，但酶是游离于溶液中而非包裹在红细胞内。红细胞和天冬酰胺酶分别用51Cr和125I进行标记。负载酶的重封红细胞的循环半衰期为7天，而对照红细胞为9天。从第5天开始，注射负载天冬酰胺酶红细胞的猴子体内循环酶活性比对照组高出几个数量级。负载药物的红细胞明显靶向到脾脏和肝脏。单次静脉注射负载天冬酰胺酶红细胞的猴子血清中天冬酰胺酶底物水平的抑制时间为20天，是对照猴子的两倍。结果显示，在红细胞包裹天冬酰胺酶的猴子体内，抗天冬酰胺酶抗体的产生达到更高水平且持续时间更长。还获得了证据表明，将天冬酰胺酶包裹在红细胞中可防止豚鼠发生过敏反应。因此，这种药物递送系统也被提议作为一种避免危及生命的过敏反应的策略。本文讨论了红细胞负载作为药物递送系统的优缺点。
