Polymer Blend Controls Nanoparticles' Surface Charge for Improved Mucus Penetration and Epithelial Cell Adhesion

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Mucus forms a significant barrier to nanoparticle (NP) drug delivery across epithelial surfaces.
• Mucus traps nanoparticles, hindering their access to target cells and limiting therapeutic efficacy.

Purpose of the Study:

• To engineer mucus-evading yet cell-sticky (MECS) nanoparticles for enhanced mucosal drug delivery.
• To overcome the inherent trade-off between mucus penetration and cellular adhesion in nanoparticle design.

Main Methods:

• Developed 100-nanometer MECS nanoparticles using Flash Nanoprecipitation.
• Incorporated polycationic poly(dimethylaminoethyl methacrylate) (PDMAMA) into a neutral poly(ethylene glycol) (PEG) corona.
• Evaluated nanoparticle performance using in vitro cell cultures and gut-on-a-chip organoid models.

Main Results:

• MECS nanoparticles demonstrated effective mucus penetration, comparable to purely PEGylated controls.
• MECS nanoparticles exhibited a 45-fold increase in binding to epithelial cells compared to controls.
• The dual functionality of mucus evasion and cell adhesion was confirmed in both cell cultures and organoids.

Conclusions:

• The developed MECS nanoparticles offer a versatile strategy for improving drug delivery across mucosal barriers.
• This approach successfully addresses the challenge of balancing mucodiffusion and cellular uptake for enhanced therapeutic delivery.
• MECS nanoparticles represent a promising advancement in overcoming biological barriers for targeted drug delivery applications.