Microrheology of Ionic Liquid Doped Mucus for an Efficient Delivery of Protein‐Based Oral Drugs

Abstract Developing protein‐based drugs for oral administration is one of the most challenging aspects of research due to their low stability and inability to permeate through intestinal mucus barrier. Recent studies suggest that the ionic liquids (ILs) can combine with protein‐based drugs to improve stability and mucus‐penetration capabilities. However, the interactions among protein‐based drugs, ILs, and mucin are rather unknown, which can play a pivotal role in such drug delivery. The present work unveils the molecular mechanisms of the delivery of protein‐based drugs, with the help of microrheology experiments and density functional theory (DFT) simulations. The study employs a model mesoscale drug delivery system composed of an IL, mucin, and bovine serum albumin (BSA) as a model drug. In particular, following the microrheological changes of such drug formulations helps in tracing the molecular interactions such as electrostatic, van der Waals, steric, and hydrogen bonds, at the various stages of BSA, mucin, and IL assemblage. The results are corroborated by the morphological studies using atomic force microscopy supplemented by microrheological studies using diffusing‐wave‐spectroscopy. A human intestine has also been simulated as a biomimetic in‐vitro prototype to demonstrate stability and penetration of BSA through mucin in the presence of IL.