Heat-Induced Structural Changes in Lactoferrin for Enhanced Mucoadhesion

TL;DR

This study shows that heating lactoferrin changes its structure, making it better at sticking to mucus, which could improve drug delivery.

Contribution

The novel finding is that heat-induced structural changes in lactoferrin enhance mucoadhesion through hydrophobic interactions.

Findings

Heat treatment at 95 °C increases lactoferrin's affinity for mucin.

Mucoadhesion is driven by hydrophobic interactions, not disulfide bonds.

Lactoferrin-mucin complexes show high surface activity and shear-thinning behavior.

Abstract

The development of
biocompatible and safe mucoadhesive materials
is critical for improving therapeutic strategies, where cationic proteins
such as lactoferrin are emerging as promising alternatives to synthetic
polymers. Here, we demonstrate how thermal denaturation of lactoferrin
can be used as a viable strategy to enhance mucoadhesion. We identify
and study in detail the structural changes in lactoferrin upon thermal
denaturation using light scattering, circular dichroism spectroscopy,
gel-electrophoresis, and atomic force microscopy. Lactoferrin-mucin
binding was evaluated using rheology, confocal microscopy, and quartz
crystal microbalance with dissipation monitoring. We find that lactoferrin
binds to mucin at its native state, heat-treatment at 95 °C enhances
its affinity for mucin, and that the adhesion mechanism relies on
hydrophobic interactions with no obvious contributions of disulfide
bonds. Lactoferrin and its resulting complexes with mucin present
high surface activity, which induces an artificial shear-thinning
rheological response. While electrostatic interactions have been considered
the dominant mucoadhesive mechanism of native lactoferrin up to now,
our findings highlight the role of hydrophobic interactions, providing
a design route to alter the structural state of the protein to inspire
the development of future natural protein-based mucoadhesive systems.

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