INFUSION OF RED-BLOOD-CELL LOADED ASPARAGINASE IN MONKEY - IMMUNOLOGICAL, METABOLIC, AND TOXICOLOGIC CONSEQUENCES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 101  (5) , 679-691
Abstract
In order to evaluate enzyme loading of RBC [red blood cells] as a drug delivery system, the antitumor agent asparaginase was loaded into the erythrocytes of 9 monkeys at 3 different doses and autologously injected back into these animals. Nine control monkeys were also once injected i.v. at the same doses of enzyme, but the enzyme was free in solution rather than entrapped in RBC. The RBC and asparaginase were labeled 51Cr and 125I, respectively. The circulating half-life of the enzyme-loaded, resealed RBC was 7 days, as compared to 9 days in the control RBC. 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 RBC into the spleen and liver was apparent. Suppression of the serum substrate level of asparaginase in the monkeys treated with the single i.v. injection of RBC loaded with asparaginase was 20 days, which was twice as long as the suppression in the control monkeys. Production of anti-asparaginase antibody reached a higher level and persisted longer in the monkeys with RBC-entrapped asparaginase. Entrapping asparaginase in RBC protects against anaphylaxis in the guinea-pig. This drug delivery system is proposed as a strategy to avoid life-threatening allergic reactions. Advantages and limitations of RBC loading as a drug delivery system are discussed.