Mechanistic Influence of Polymer Species, Molecular Weight, and Functionalization on Mucin–Polymer Binding Interactions
Why this work is in the frame
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Bibliographic record
Abstract
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 that the addition of methyl groups to cellulose derivatives induces a unique binding fingerprint. Next, we expanded the mucoadhesive polymer series to include CMC, HPC, HPMC, poly(acrylic acid) (PAA), and poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) and observed a negative correlation between molecular weight and mucoadhesive interaction intimacy, highlighting the differences across polymer species. Finally, we explored polymers that lack mucin interactions to illustrate the limitations of polymer composition and molecular weight as predictors of mucoadhesive fate. Altogether, these experiments were used to report on mucoadhesive interactions at the atomic level and revealed that polymer design is dependent on both the availability and accessibility of mucoadhesive functional groups.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it