title: Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid).
abstract: Mucus secretions coating entry points to the human body that are not covered by skin efficiently trap and clear conventional drug carriers, limiting controlled drug delivery at mucosal surfaces. To overcome this challenge, we recently engineered nanoparticles that readily penetrate a variety of human mucus secretions, which we termed mucus-penetrating particles (MPP). Here, we report a new biodegradable MPP formulation based on diblock copolymers of poly(lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA-PEG). PLGA-PEG nanoparticles prepared by a solvent diffusion method rapidly diffused through fresh, undiluted human cervicovaginal mucus (CVM) with an average speed only eightfold lower than their theoretical speed in water. In contrast, PLGA nanoparticles were slowed more than 12,000-fold in the same CVM secretions. Based on the measured diffusivities, as much as 75% of the PLGA-PEG nanoparticles are expected to penetrate a 10-μm-thick mucus layer within 30 min, whereas virtually no PLGA nanoparticles are expected to do so over the same duration. These results encourage further development of PLGA-PEG nanoparticles as mucus-penetrating drug carriers for improved drug and gene delivery to mucosal surfaces.
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Craig
authors.initials: C
authors.lastname: Schneider
authors.forename: Weixi
authors.initials: W
authors.lastname: Zhong
authors.forename: Sarah
authors.initials: S
authors.lastname: Pulicare
authors.forename: Woo-Jin
authors.initials: WJ
authors.lastname: Choi
authors.forename: Olcay
authors.initials: O
authors.lastname: Mert
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Lai
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
keywords: Drug delivery; Human mucus; Mucus-penetrating particles