Enhanced Oral Delivery of Insulin via Loading in Polysorbate-80 Micelles

Oral delivery of insulin exhibits low bioavailability due to the hydrolysis in acidic gastric juice, biodegradation of enzymes, and inefficient penetration through the intestinal mucus and epithelial cell layer. Here, we report a micelle platform to enhance the oral delivery of insulin. Insulin was precipitated by zinc ions to form hydrophobic nanoparticles and subsequently coated with a surfactant polysorbate-80 (Tween-80) to form nanosized micelles (TW-Zn-rhINS). Tween-80 protects the insulin from the degradation of enzymes, meanwhile facilitating the diffusion within mucus and the epithelial cell layer by opening the tight junctions. The micelles were then lyophilized and encapsulated in enteric capsules to overcome acidic hydrolysis in gastric juice. The micelles significantly increased transcellular insulin transport and uptake. The in vivo experiments demonstrated that oral TW-Zn-rhINS micelle capsules (30 IU/kg) decreased the blood glucose of diabetic mice by 58.74% after administration for 6 h, while the postprandial blood glucose dropped by 51.1%. Pharmacokinetics data indicated that the relative oral bioavailability of TW-Zn-rhINS was 7.88%, which was 7.73 times higher than that of insulin. The micelles present a promising platform to enhance the oral bioavailability of insulin, also indicating a potential for oral delivery of protein.