The Great Mucus Barrier

Abstract

Biomaterials![Figure][1] CREDIT: L. M. ENSIGN ET AL., SCI. TRANSL. MED. , 4 , 138RA79 (2012) Mucus is often thought of as a nuisance when you have a bad cold or runny nose, but this is only one aspect of its broader use by the body to filter out foreign materials. Its tenacity in grabbing onto particulate matter also makes it difficult to deliver drugs to tissues that are protected by a mucus layer, such as the vaginal tissues, but delivery and sustained dosing to this region could aid in the prevention of sexually transmitted diseases or cervical cancer. Ensign et al. designed mucus-penetrating particles by coating either carboxylic acid–coated polystyrene nanoparticles or poly(lactic-co-glycolic acid) nanoparticles with a dense layer of polyethylene glycol. When administered in a hypotonic solution to mice, the regular particles got trapped in the cervicovaginal mucus layer, whereas the coated particles covered the entire vaginal epithelium, including that of the vaginal folds, in less than 10 min. In tests on the delivery of small molecules using the particles as part of a vaginal gel, the coated particles showed not only greater but also much more uniform coverage, and there was retention of the small molecules a full day after administration. In a final demonstration, modified acyclovir, a drug for treating herpes simplex 2, was loaded into the particles and compared with a soluble form of the drug. Whereas almost 90% of the mice became infected with HSV2 in the latter case, the drug-loaded coated particles provided protection for more than half the mice. Sci. Transl. Med. 4 , 138ra79 (2012). [1]: pending:yes