From Mucin to Smart Medicine: Engineering Mucin-Based Biomaterials for Advanced and Responsive Drug Delivery.

Abstract

Mucin, a highly glycosylated macromolecular component of mucus, has traditionally been regarded as a biological barrier that restricts drug transport across mucosal surfaces. Growing evidence, however, has repositioned mucin as a functional and engineerable biomaterial with distinctive potential for advanced drug delivery. This review examines the evolution of mucin-based delivery systems from native mucin and bulk matrices to engineered hydrogels, hybrid materials, micro- and nanoparticles, and intrinsically glycosylated nanocarriers such as mucosomes. Particular emphasis is placed on the relationship between mucin molecular architecture and pharmaceutical functionality and on the engineering strategies used to control its material properties, including chemical modification, crosslinking, polymer hybridization, nanoscale assembly, and molecular programming. These approaches have progressively transformed mucin-based systems from passive drug reservoirs into environmentally responsive and increasingly programmable platforms capable of controlled release, molecular recognition, and on-demand therapeutic responses. Emerging applications in mucosal and ocular delivery, antimicrobial and biofilm therapy, biologics, and nucleic acid therapeutics further demonstrate the expanding pharmaceutical potential of mucin. Nevertheless, clinical translation remains constrained by source-dependent heterogeneity, variability in glycosylation and purification, batch-to-batch reproducibility, stability, sterilization, scalable manufacturing, and limited in vivo validation. Future progress will require better-defined mucin materials, standardized characterization and manufacturing, rigorous safety and efficacy assessment, and demonstration of clear therapeutic advantages over established delivery systems. Collectively, advances in mucin engineering, glycoengineering, nanotechnology, and molecular programming may enable the transition of mucin from a biological barrier component to a responsive, programmable, and clinically relevant platform for smart drug delivery.

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