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A Strategic Blend of Stabilizing Polymers to Control Particle Surface Charge for Enhanced Mucus Transport and Cell Binding

Stevens, C. A.; Sevarika, B.; Wilson, B. K.; Wang, C.-M.; Carcamo-Oyarce, G.; Degen, G.; Kassis, T.; Lehr, C. M.; Carrier, R.; Ribbeck, K.; Prud'homme, R. K.

2024-09-19 biophysics
10.1101/2024.09.17.613453 bioRxiv
Show abstract

Mucus layers, viscoelastic gels abundant in anionic mucin glycoproteins, obstruct therapeutic delivery across all mucosal surfaces. We found that strongly positively charged nanoparticles (NPs) rapidly adsorb a mucin protein corona in mucus, impeding cell binding and uptake. To overcome this, we developed mucus-evading, cell-adhesive (MECS) NPs with variable surface charge using Flash NanoPrecipitation, by blending a neutral poly(ethylene glycol) (PEG) corona for mucus transport with a small amount, 5 wt%, of polycationic dimethylaminoethyl methacrylate (PDMAEMA) for increased cell targeting. In vitro experiments confirmed rapid mucus penetration and binding to epithelial cells by MECS NPs, suggesting a breakthrough in mucosal drug delivery.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

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14
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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.