Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 46; pp. 19268 - 19273
• Main Authors: Tang, Benjamin C, Dawson, Michelle, Lai, Samuel K, Wang, Ying-Ying, Suk, Jung Soo, Yang, Ming, Zeitlin, Pamela, Boyle, Michael P, Fu, Jie, Hanes, Justin
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.11.2009; National Acad Sciences
• Series: From the Cover
• Subjects: Anhydrides - chemistry; Anhydrides - metabolism; biodegradability; Biodegradation; Biological Sciences; Biopolymers; Cervix Mucus - metabolism; Coatings; composite polymers; cystic fibrosis; Cystic Fibrosis - metabolism; Diffusion coefficient; Drug Carriers - chemistry; Drug Carriers - metabolism; drug delivery systems; drugs; eyes; Female; females; gastrointestinal system; Gastrointestinal tract; gene transfer; Human subjects; Humans; Latex; Lungs; mucosa; Mucous membrane; Mucus; Nanoparticles; nasopharynx; Particle diffusion; patients; polyethylene glycol; Polyethylene Glycols - chemistry; Polyethylene Glycols - metabolism; Polymers; Secretion; Sputum; Sputum - metabolism; viscoelasticity; Viscosity
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0905998106

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.