Effect of Orally Administered Glutathione-Montmorillonite Hybrid Systems on Tissue Distribution

Abstract

An ubiquitous tripeptide, glutathione (GSH), is assigned a role in detoxification, activation of immune system, intermediary metabolism, transport, and protection of cells against free radicals or reactive oxygen species. However, instability of orally administered GSH in gastrointestinal (GI) tract leads to low absorption and low bioavailability in tissues. In this study, we attempted to synthesize GSH-montmorillonite (MMT) hybrid systems by intercalating GSH into the interlayers of a cationic clay delivery carrier, MMT, to improve GSH bioavailability at the systemic level. Polymer coating of the hybrid with polyvinylacetal diethylaminoacetate (AEA) was further performed to obtain better stability. Synthetic condition of both GSH-MMT and AEA-GSH-MMT hybrids was optimized, and then GSH-delivery efficiency was evaluated in various organs after oral administration in normal as well as GSH-deficient mice. The present GSH-MMT hybrids remarkably enhanced GSH concentration in the plasma, heart, kidney, and liver, especially when AEA-GSH-MMT hybrid was administered under GSH-deficient condition. Moreover, both hybrids did not induce acute oral toxicity up to 2000 mg/kg, suggesting their great potential for pharmaceutical application.