Cationic β‐Cyclodextrin Platforms for Oral Insulin Delivery: Supramolecular Host–Guest Chemistry Meets Polymer Engineering, Mucosal Transport, and Translational Manufacturing

ABSTRACT Nonphysiological insulin distribution owing to the evasion of first‐pass effects, resulting in an unpredictable absorption and increased risk of hypoglycemic episodes, is considered a major challenge associated with subcutaneous administration of insulin. Hence, the development of orally administrable insulin formulations is inevitable, albeit the apparent risk of their instability in GI tract combined with a poor epithelial permeability is highly formidable. Cationic β‐CD offers dual advantage for the accomplishment of oral delivery of insulin, pertaining to its stability toward degradation in GI tract and mucoadhesion potential (depending on the nature of cationic appendage), which result in improved bioavailability and prolonged hypoglycemic effect. The modification is done either by appending the cationic polymers to the parent β‐CD ring or introducing a cationic moiety by chemical modification of the parent β‐CD structure. In this review, a systematic account on the recent developments in cationic β‐CD‐based carriers for enhancing oral delivery of insulin has been presented.