Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal
(GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including
conventional particle-based drug delivery systems, are efficiently trapped in human
mucus layers by steric obstruction and/or adhesion. Trapped particles are typically
removed from the mucosal tissue within seconds to a few hours depending on anatomical
location, thereby strongly limiting the duration of sustained drug delivery locally.
A number of debilitating diseases could be treated more effectively and with fewer
side effects if drugs and genes could be more efficiently delivered to the underlying
mucosal tissues in a controlled manner. This review first describes the tenacious
mucus barrier properties that have precluded the efficient penetration of therapeutic
particles. It then reviews the design and development of new mucus-penetrating particles
that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained
drug delivery for localized therapies in mucosal tissues.