Mucus Penetrating Nanoparticles: Biophysical Tool and Method of Drug and Gene Delivery

We demonstrated that nanoparticles as large as 500 nm can diffuse rapidly through undiluted human cervicovaginal mucus, if densely coated with low molecular weight polyethylene glycol

Laura M. Ensign; Craig Schneider; Jung Soo Suk; Richard Cone; Justin Hanes

2012

Scholarcy highlights

  • Mucus is a viscoelastic, adhesive gel that coats all exposed epithelial surfaces not covered by skin, such as those of the respiratory, gastrointestinal, and female reproductive tracts, and the surface of the eye
  • After confirming that mucus penetrating particles rapidly penetrate mouse vaginal mucus, we demonstrated that MPP coat the vaginal and cervical epithelium, whereas mucoadhesive conventional mucoadhesive nanoparticles aggregated in the lumen unless the mucus was removed prior to particle administration
  • Both polystyrene-based and biodegradable MPP composed of entirely Generally Regarded as Safe ingredients were able to rapidly penetrate chronic rhinosinusitis mucus, and sputum expectorated from Cystic Fibrosis patients 27
  • We previously found that diffusion rates of 200 and 500 nm MPP were ~15-fold and ~400-fold slower in cystic fibrosis sputum than their rates in cervicovaginal mucus, likely due to increased adhesivity and steric obstruction from the sticky and dense CF sputum mesh 33
  • We used densely polyethylene glycol-coated polystyrene MPP probes to evaluate the microviscosity of CF sputum and found the microviscosity experienced by 200 nm MPP was 300–1500 times lower than the bulk viscosity, in stark contrast to the results observed with unmodified PS beads45
  • Mucin proteins form a porous mesh that traps foreign particulates via both steric and adhesive interactions. It is these properties that can reduce the efficiency of drug and gene delivery to mucosal surfaces
  • Understanding and overcoming the mucus barrier, while maintaining native barrier function, can significantly improve prophylactic and therapeutic treatments for a wide array of epithelial diseases and conditions afflicting the eye, female reproductive tract, the respiratory tract, and the gastrointestinal tract

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