EFFECT OF LIPOSOME AND CYCLODEXTRIN ENTRAPMENT ON RETARDATION OF GLUTATHIONE DECOMPOSITION OF NITROIMIDAZOLYL SULFONES

A new class of radiosensitizing pharmaceuticals derived from 4‐nitro‐5‐imidazolyl sulfones has its clinical potential compromised by a metabolic reaction with plasma glutathione which leads to a much less active metabolite. Entrapment of two members of the class in three different liposomes, one polymerized liposome, and a β‐cyclodextrin system has shown that this glutathione condensation can be suppressed by a rate factor of nearly 50‐fold. Stabilizations of these metabolically labile radiosensitizers appear to relate to their lipid‐buffer partition coefficients and to the fluidity of the liposome membrane in which they are entrapped. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company