Ionic liquid-mediated delivery of insulin to buccal mucosa

Buccal drug delivery offers a potential non-invasive means of delivering therapeutics to patients. Despite the promise, the feasibility of transporting proteins and peptides into systemic circulation from buccal administration remains a daunting challenge. Here, we report the fabrication of a biodegradable polymeric patch for buccal delivery of insulin using chitosan as the mucoadhesive matrix and ionic liquids (ILs)/deep eutectic solvent (DES) as the transport facilitator. Insulin is mixed with ILs/DES made from Choline and Geranic acid (CAGE) to form a viscoelastic CAGE gel and sandwiched between two layers of a biodegradable polymer. The rheological properties of the CAGE gel were dominated by the elastic modulus and suggested a solid-like viscoelastic behavior. CAGE induced a 7-fold increase in the cumulative insulin transport across the ex vivo porcine buccal tissue (similar to 26% of loaded insulin) which was also confirmed by confocal microscopy. The CAGE/insulin patches placed in the rat buccal pouch in vivo lowered blood glucose levels in a dose-dependent manner (up to 50% drop recorded) with no obvious tissue damage at the application site. The pharmacokinetic performance of the delivered insulin indicated a sustained profile as serum insulin levels plateaued after 3 h for the duration of study. The safety and efficacy of the polymeric patch using insulin as a model drug holds significant promise as a platform technology to deliver injectables through the buccal route.