Modification Of Inflammatory And Alzheimer Markers With Intracellular Delivery Of Insulin Using Cholestosomes

The importance of glucose metabolic changes and inflammatory responses to these changes connect diabetes and Alzheimer’s disease (AD). The role intracellular insulin may have in this process could provide for alternative therapeutic approaches. In this study a novel cholesteryl ester based vesicle called a CholestosomeTM, that encapsulates payloads at a high drug to lipid ratio has been used to study the effect of intracellular delivery of insulin on the expression of AD and inflammatory markers in neural cell lines. CholestosomeTM-encapsulated molecules, including insulin, have been delivered to a number of different cell types in vitro and in vivo. Prior studies in rodents have shown the potential for oral delivery of insulin using cholestosomeTM technology with a high tissue to plasma ratio in several tissues, including brain. The present study measured the relative expression of AD (APP, BACE, presenilin 1 and 2, clusterin and GSK3B) and inflammatory (MMP-9, TLR-4, IL-1beta and TNF-alpha) markers determined after delivery of Insulin (I) and CholestosomeTM encapsulated insulin (CHI) to several neural cell lines. In this preliminary comparative study the impact of insulin (I) versus CHI on RNA expression of these markers differed depending on neural subtype and marker type. Disclosure M. McCourt: None. L. Mielnicki: None. J. Hughes: None. M.Q. Irving: None. J. Schentag: Stock/Shareholder; Self; TheraSyn. H. Ghanim: None. P. Dandona: Research Support; Self; JDRF. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc.