Interactions of Mucins with Biopolymers and Drug Delivery Particles

Sammanfattning: The main components in the mucous gels apart from water are mucins, which are proteins with high molecular weights and an abundance of negatively charged oligosaccharide side chains. The aim of the investigations was to characterize interactions between mucins and other proteins that are present in the mucous gel, and also between mucins and components used in pharmaceutical formulations. More specifically, the main objectives were (I) to investigate the possibility to assemble multilayer films with mucins and oppositely charged polymers or proteins on solid substrates; (II) to evaluate mucoadhesive proper-ties of drug delivery particles by examination of their interactions with mucins. The construction of multilayer films was performed on silica and hydrophobized silica surfaces by alternate adsorption, and the adsorbed amount and thickness of the films were measured in situ by time resolved ellipsometry. It was demonstrated that films could be assembled using mucins in combination with both chitosan and lactoperoxidase. The build-up was characterized by adsorption and redissolution processes, and the extent of redissolution could be explained by taking the charge densities and concentrations of the components into account. It was also demonstrated that the nature of the substrate can be crucial for the possibilities to assemble multilayer films, and from the results it may be concluded that a high amount of mucin in the first step is important for successful layer-by-layer assembly. Furthermore, it was demonstrated that lactoperoxidase is catalytically active when adsorbed to mucin layers, and it may thereby exert its antimicrobial action. The evaluation of mucoadhesive properties of drug delivery particles was performed with lipid nanoparticles stabilized by a poly(ethylene oxide) based polymer and with particles modified by chitosan. Both types of model particles (unmodified and chitosan modified) were investigated by measuring their adsorption to mucin-coated silica surfaces by ellipsometry. It was shown that the binding of unmodified particles to mucin-coated silica surfaces was weak and pH-dependent. Based on the pH and electrolyte dependence of the adsorption, it was proposed that the interaction is mediated by hydrogen bonding between protonated carboxyl groups in the mucin molecule and oxygen atoms in poly(ethylene oxide). Chitosan modified particles, on the other hand, showed a substantial and strong binding to mucin-coated surfaces, which can probably be attributed to interactions between amino groups in chitosan and negatively charged groups in the mucin layer. The findings from the present investigations are in agreement with previous reports on the interaction of mucins with poly(ethylene oxide) and chitosan. It can therefore be concluded that the methodology applied is useful for evaluating mucoadhesive properties of nanoparticles.