Enhanced intracellular stability and efficacy of PEG modified dextranase in the treatment of a model storage disorder

Abstract

A model for storage disorders was produced in the livers of mice by the 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 covalently modified with PEG, and liposomes were used as carriers for delivering the free and the modified enzyme to the liver at similar rates. The PEG-dextranase conjugate showed greater intracellular stability as compared to the native enzyme. Liposomally delivered PEG-dextranase, by virtue of its enhanced intracellular stability, could not only degrade the accumulated FITC-dextran, but could also prevent its further accumulation over a period of time. This enhanced intracellular stability of enzymes would be of importance in extending the catalytic life of therapeutically active enzymes and thereby improve their therapeutic potential for the treatment of intracellular storage disorders.