Biodegradable Nanoparticles Composed Entirely of Safe Materials that Rapidlly Penetrate Human Mucus

摘要

Mucus is a highly viscoelastic and adhesive substance that protects against infection and injury at nearly all entry points to the body not covered by skin. However, mucus also traps potentially life-saving drugs and nucleic acids delivered by synthetic nanoparticles, including those composed of poly-(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL), two FDA-approved polymers commonly used in drug-delivery applications. Trapped particles, with diffusivities in mucus several-thousand-fold lower than in water, do not efficiently reach the deeper mucus layers that are cleared much more slowly, or the underlying epithelium, and are thus eliminated by mucus clearance mechanisms (on the order of seconds to a few hours depending on anatomical site). For sustained or targeted drug delivery' to mucosal surfaces, nanoparticles must quickly penetrate mucus gels, a longstanding challenge in drug delivery.