Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Benjamin C. Tang, Michelle Dawson, Samuel K. Lai, Ying Ying Wang, Jung Soo Suk, Ming Yang, Pamela Zeitlin, Michael P. Boyle, Jie Fu, Justin Hanes

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)19268-19273
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number46
DOIs
StatePublished - Nov 17 2009

Keywords

  • Cystic fibrosis
  • Drug delivery
  • Gene therapy
  • Mucosa
  • Mucus-penetrating particle

ASJC Scopus subject areas

  • General

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