ENHANCED INTRACELLULAR STABILITY AND EFFICACY OF PEG-MODIFIED DEXTRANASE IN THE TREATMENT OF A MODEL STORAGE DISORDER

A model for storage disorders was produced in the livers of mice by th e administration of liposomally encapsulated FITC-dextran. Liposomally delivered dextranase was found to be more efficient in degrading the accumulated substrate as compared to the free enzyme. Dextranase was c ovalently modified with PEG, and liposomes were used as carriers for d elivering the free and the modified enzyme to the liver at similar rat es. The PEG-dextranase conjugate showed greater intracellular stabilit y as compared to the native enzyme. Liposomally delivered PEG-dextrana se, by virtue of its enhanced intracellular stability, could not only degrade the accumulated FITC-dextran, but could also prevent its furth er accumulation over a period of time. This enhanced intracellular sta bility of enzymes would be of importance in extending the catalytic li fe of therapeutically active enzymes and thereby improve their therape utic potential for the treatment of intracellular storage disorders.