Allen T M, Murray L, Bhardwaj D, Poznansky M J
J Pharmacol Exp Ther. 1985 Jul;234(1):250-4.
Enzyme albumin conjugates have been proposed as a means of increasing the efficacy of enzyme use in vivo and decreasing immune response to the enzyme. Particulate drug carriers, however, have a pronounced tendency to localize in the mononuclear phagocyte (reticuloendothelial) system. We have examined in mice the effect on phagocytic index, tissue distribution and organ size of continued administration of conjugates of alpha-glucosidase with either homologous or heterologous albumin. Mice received 10 X 2-mg injections of bovine serum albumin (BSA) or mouse serum albumin (MSA), either free, polymerized or conjugated with alpha-glucosidase. Experiments involving BSA had to be terminated before the end of the experiment because of anaphylaxis, but these reactions were less severe to the polymerized albumin than to free albumin. Free BSA, BSA polymer and BSA-enzyme conjugates all caused a decrease in phagocytic index after six injections. Mice receiving MSA showed no evidence of anaphylaxis, but mice receiving six or more injections of free MSA, MSA polymer or MSA-enzyme conjugate had significantly decreased phagocytic indices as compared to controls. Phagocytic indices had returned to normal by 7 days after the final injection. Tissue distribution of 125-I-labeled albumin preparations was determined in either naive or chronically injected mice.
酶白蛋白缀合物已被提议作为一种提高酶在体内使用效率并降低对该酶免疫反应的方法。然而，颗粒药物载体有明显的倾向定位于单核吞噬细胞（网状内皮）系统。我们在小鼠中研究了持续给予α-葡萄糖苷酶与同源或异源白蛋白的缀合物对吞噬指数、组织分布和器官大小的影响。小鼠接受10次2毫克的牛血清白蛋白（BSA）或小鼠血清白蛋白（MSA）注射，分别为游离的、聚合的或与α-葡萄糖苷酶缀合的。涉及BSA的实验因过敏反应在实验结束前不得不终止，但这些反应对聚合白蛋白的严重程度低于游离白蛋白。在六次注射后，游离BSA、BSA聚合物和BSA-酶缀合物均导致吞噬指数下降。接受MSA的小鼠没有出现过敏反应的迹象，但与对照组相比，接受六次或更多次游离MSA、MSA聚合物或MSA-酶缀合物注射的小鼠吞噬指数显著降低。在最后一次注射后7天，吞噬指数恢复正常。在未注射或长期注射的小鼠中测定了125-I标记白蛋白制剂的组织分布。
