Lateral Assessment of Mucomimetic Hydrogels to Evaluate Correlation between Microscopic and Macroscopic Properties

A major limitation in the development of mucosal drug delivery systems is the design of in vitro models that accurately reflect in vivo conditions. Traditionally, models seek to mimic characteristics of physiological mucus, often focusing on property‐specific trial metrics such as rheological behavior or diffusion of a nanoparticle of interest. Despite the success of these models, translation from in vitro results to in vivo trials is limited. As a result, several authors have called for work to develop standardized testing methodologies and characterize the influence of model properties on drug delivery performance. To this end, a series of trials is performed on 12 mucomimetic hydrogels reproduced from literature. Experiments show that there is no consistent correlation between barrier performance and rheological or microstructural properties of the tested mucomimetic hydrogels. In addition, the permeability of both mucopenetrating and mucoadhesive nanoparticles is assessed, revealing non‐obvious variations in barrier properties such as the relative contributions of electrostatic and hydrophobic interactions in different models. These results demonstrate the limitations of predicting mucomimetic behavior with common characterization techniques and highlight the importance of testing barrier performance with multiple nanoparticle formulations. Permeabilities of both mucopenetrating and mucoadhesive nanoparticles are tested against 12 synthetic mucus models drawn from literature. Data reveal that there is no consistent correlation between the tested material properties of the models and their resulting barrier performance. Nonobvious variations in electrostatic and hydrophobic contributions reinforce the need to test models directly against different nanoparticles to assess their behavior more completely.