Abstract

Oral delivery of biologic drugs is a highly desired yet challenging goal because of the many barriers posed by the GI tract. Ionic liquids (ILs) and deep eutectic solvents (DESs) such as choline and geranate (CAGE) have demonstrated the potential to improve intestinal absorption of insulin and poorly soluble drugs. As with other delivery agents, localization of the ILs in the intestine can enhance the delivery potential by increasing local concentrations while maintaining low off-target concentrations, thus improving the therapeutic window of the ILs. Here, we describe a method of encapsulating CAGE into a gel using PVA, forming a mucoadhesive ionogel patch (CAGE-patch) designed to adhere to the intestine. CAGE-patches formed via repeated freeze-thaw cycles demonstrated mucoadhesive strength, swelling, and controlled release of both CAGE and insulin. In vitro transport studies revealed a more than 30% increase in insulin transport when compared to controls across Caco-2 and HT29-MTX-E12 coculture layers. This design provides a novel approach to localize ionic liquids and therapeutics in the GI tract for enhanced oral delivery.

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