Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

• DOI: 10.1073/pnas.0905998106
• Publication Date: 2009-11-10T03:20:09Z
• Authors: 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
• Keywords: PLGA; Sebacic acid; Biodegradable polymer; Mucoadhesion; Glycolic acid

Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, female reproductive thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal a significant rate. We prepared nanoparticles diblock copolymer poly(sebacic acid) poly(ethylene glycol) (PSA-PEG), both which are routinely used in humans. In fresh undiluted (CVM), bulk viscosity approximately 1,800-fold higher than water low shear, PSA-PEG diffused an average speed only 12-fold lower same pure water. contrast, similarly sized PSA or poly(lactic-co-glycolic (PLGA) least 3,300-fold slower CVM also penetrated sputum expectorated lungs patients with cystic fibrosis, disease characterized by hyperviscoelastic secretions. Rapid nanoparticle transport is made possible efficient partitioning PEG particle surface during formulation. Biodegradable polymeric capable overcoming barriers providing sustained release open improved gene