Mechanistic Influence of Polymer Species, Molecular Weight, and Functionalization on Mucin–Polymer Binding Interactions

作者：Jeffrey Watchorn, Samantha Stuart, Darcy C. Burns, Frank Gu · 发表于：ACS Applied Polymer Materials · 年份：2022 · DOI：10.1021/acsapm.2c01220 · 被引用次数：21 · 研究领域：Advanced Drug Delivery Systems、Glycosylation and Glycoproteins Research、Carbohydrate Chemistry and Synthesis

Improving both systemic and localized delivery of pharmaceuticals by optimizing the delivery vehicle properties is a major area of ongoing research. One such engineered property is mucoadhesion, wherein polymers are tailored to optimize polymer–mucin interactions to increase drug residence times and uptake efficiency. There are many examples of mucoadhesion as a drug delivery modality in the literature, yet the underlying mechanisms remain poorly understood, and its clinical translation is limited. Within this mechanistic lens, we found that nuclear magnetic resonance (NMR) is a powerful tool for uncovering polymer–mucin interactions. We investigated the influence of several polymer design parameters including molecular weight and repeating unit functionalization on mucoadhesion and uncovered several key findings in terms of the influence of these design parameters on polymer–protein intermacromolecular interactions. First, we probed individual polymer species including hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), and carboxymethyl cellulose (CMC) and identified that molecular-weight-driven changes in the polymer–mucin interaction fingerprint result from perturbations in the polymer-specific binding complex. Specifically, we found that CMC and HPC complexes spatially reorient with increasing molecular weight, whereas HPMC complexes do not. We expanded this comparison to include functional group changes to the polymer repeating unit, where we showed th...