title: Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier.
abstract: Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water at low shear, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lactic-co-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Tang
authors.forename: Michelle
authors.initials: M
authors.lastname: Dawson
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Lai
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Suk
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Pamela
authors.initials: P
authors.lastname: Zeitlin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Boyle
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
mesh_terms: D000812:Anhydrides / Q000737:chemistry / Q000378:metabolism*; D002582:Cervix Mucus / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism
chemical_list: D000812:Anhydrides; D004337:Drug Carriers; C405032:poly(sebacic anhydride)-b-polyethylene glycol; D011092:Polyethylene Glycols