Thermodynamic and Conformational Study on the Interaction between pH-Responsive Polymer-Shell Cubosome and Mucin for Drug Delivery Applications

The physiological approach of mucosal sites as a systemic therapeutic reach is of paramount medical and pharmaceutical interest. Mucin is a principal component of mucosal sites, playing a crucial role in protecting the epithelial tissues from chemical and mechanical stress and impeding damage and infections. Hence, the efficiency of mucosal-targeted drug delivery materials passes through a challenging mucin environment. In this study, we explored the thermodynamics of interaction and consequent conformational changes of mucin complexing with polymer-shell cubosomes─hybrid core–shell nanoparticles of pH-responsive features and conceived for oral drug delivery applications. The complexation was in situ monitored in strong acid media at pH 2.5 and in slightly alkaline pH 7.4, using isothermal titration calorimetry, while colloidal size and surface potential were considered to support the disclosure of the thermodynamic process. Further using differential scanning calorimetry and synchrotron far-UV circular dichroism spectroscopy, the conformational behavior of mucin regarding the nanoparticles was described, given the specificities of the macromolecule’s nature at each pH. By combining the thermodynamics of interaction with molecular conformation analysis, a descriptive scenario for the pH-driven complexation was unveiled. The study sheds light on prominent structural features that can be implicated in advancing the muco-adhesive and muco-penetrating potential of pH-sensitive nanoparticles.