Mucus‐Mimicking Mucin‐Based Hydrogels by Tandem Chemical and Physical Crosslinking

Abstract

Mucosal tissues represent a major interface between the body and the external environment and are covered by a highly hydrated mucins gel called mucus. Mucus lubricates, protects and modulate the moisture levels of the tissue and has been capitalized in transmucosal drug delivery. Pharmaceutical researchers often use freshly excised animal mucosal membranes to assess mucoadhesion and muco‐penetration of pharmaceutical formulations which may struggle with limited accessibility and ethical questions. Aiming to develop a platform for the rationale study of the interaction of drugs and delivery systems with mucosal tissues, in this work we synthesize mucus‐mimicking mucin‐based hydrogels by the tandem chemical and physical crosslinking of 4% w/v mucin aqueous solutions. Chemical crosslinking is achieved with glutaraldehyde (0.3% and 0.75% w/v), while physical crosslinking by one or two freeze‐thawing cycles. Hydrogels after one freeze‐thawing cycle show water content of 97.6‐98.1%, density of 0.0529‐0.0648 g/cm3, and storage and loss moduli of ∼40‐60 Pa and ∼3‐5 Pa, respectively, that resemble the properties of native gastrointestinal mucus. The mechanical stability of the hydrogels increased over the number of freeze‐thawing cycles. Overall results highlight the potential of this simple, reproducible and scalable method to produce artificial mucus‐mimicking hydrogels for different applications in pharmaceutical research.This article is protected by copyright. All rights reserved