Comparative effect and fate of non-entrapped and liposome-entrapped neuraminidase injected into rats.
Non-entrapped and liposome-entrapped Clostridium perfringens neuraminidase (0.5-0.6 unit) was injected into rats and its fate as well as its effect on plasma and erythrocyte N-acetylneuraminic acid was investigated. The following observations were made. (1) Although removal of both non-entrapped and liposome-entrapped neuraminidase from the circulation was completed within 5h after injection, their recovery in tissues was distinctly different; 7-10% of the injected non-entrapped enzyme was found in the liver and none in the liver lysosomal fraction or the spleen. In contrast, 20-26% of the liposome-entrapped enzyme was found in the liver of which 60-69% was in the lysosomal fraction. Spleen contained 3.6-5.0% of the enzyme. (2) The presence of the non-entrapped neuraminidase in blood led to the extensive desialylation of plasma and to a decrease in the concentration or total removal from the circulation of some of the plasma glycoproteins. (3) Injection of non-entrapped neuraminidase also led to the partial desialylation of erythrocytes the life span of which was diminished and their uptake by the liver and spleen augmented. (4) Entrapment of neuraminidase in liposomes before its injection prevented the enzyme from acting on its substrate in plasma or on the erythrocyte surface, and values obtained for plasma glycoproteins and erythrocyte survival were similar to those observed in control rats. (5) Entrapment in liposomes of therapeutic hydrolases intended for the degradation of substances stored within the tissue lysosomes of patients with storage diseases could prevent the potentially hazardous enzymic action of hydrolases in blood and at the same time direct the enzymes to the intracellular sites where they are needed.
D000818:Animals; D002498:Centrifugation; D002860:Chromium Radioisotopes; D003016:Clostridium perfringens / Q000201:enzymology; D004912:Erythrocytes / Q000187:drug effects; D007122:Immunoelectrophoresis; D007267:Injections; D008081:Liposomes / Q000378:metabolism*; D008099:Liver / Q000032:analysis; D009439:Neuraminidase / Q000378:metabolism* / Q000494:pharmacology; D010949:Plasma / Q000187:drug effects; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism; D013154:Spleen / Q000032:analysis
D002860:Chromium Radioisotopes; D008081:Liposomes; D012794:Sialic Acids; D009439:Neuraminidase