Nano LettersBiophysicsPeer-reviewed journal article
A Strategic Blend of Stabilizing Polymers to Control Particle Surface Charge for Enhanced Mucus Transport and Cell Binding
Corey Alfred StevensiD, Boris ŠevarikaiD, Brian K. Wilson, Chia-Ming WangiD, Gerardo Cárcamo‐OyarceiD, Joseph Romeo, George D. DegeniD, Timothy KassisiD, Claus‐Michael LehriD, Rebecca Lyn CarrieriD, Katharina RibbeckiD, Robert K. Prud’hommeiD
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.
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