In vivo Effects of Intraperitoneally Injected ʟ-Asparaginase Solution and ʟ-Asparaginase Immobilized within Semipermeable Nylon Microcapsules with Emphasis on Blood ʟ-Asparaginase, ‘Body’ ʟ-Asparaginase, and Plasma ʟ-Asparagine Levels

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Abstract
C3H/HEJ mice were given i.p. injections of one of the following: ʟ-asparaginase solution, microencapsulated ʟ-asparaginase, saline or control microcapsules. After injection of ʟ-asparaginase solution, enzyme activity appeared in the blood very rapidly with the highest concentration occurring after 4 h, and was then cleared from the circulation with a half-life of 4.4 h. In marked contrast, when microencapsulated ʟ-asparaginase was injected, no significant ʟ-asparaginase activity appeared in the blood for the entire duration of this study. ‘Body’ ʟ-asparaginase levels declined very rapidly with a half-life of 2 h after injection of ʟ-asparaginase solution, whereas it took 60-72 h for the ‘body' ʟ-asparaginase to decrease to 50% of the original activity after injection of microencapsulated ʟ-asparaginase. The microencapsulated ʟ-asparaginase still retained about 20% of its original activity up to 16 days after injection. Plasma ʟ-asparagine was maintained at zero concentration for 3 days after injection of ʟ-asparaginase solution, compared to 8 days after injection for microencapsulated ʟ-asparaginase. Liver ʟ-asparaginase activity was found to increase after injection of ʟ-asparaginase solution but not after injection of microencapsulated ʟ-asparaginase. The response of the host to i.p. injection of nylon microcapsules is described. Preliminary experiments indicate that the half-life for clearance of the free enzyme from the circulation of 6C3HED lymphosarcoma-bearing mice was 13.2 h as compared to 4.4 h for normal mice, and that microencapsulated ʟ-asparaginase was capable of causing regression of the tumor in the advanced, well-established stage.

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