Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Samuel K. Lai, D. Elizabeth O'Hanlon, Suzanne Harrold, Stan T. Man, Ying Ying Wang, Richard Cone, Justin Hanes

Research output: Contribution to journalArticlepeer-review

Abstract

Nanoparticles larger than the reported mesh-pore size range (10-200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (Deff) only 4- and 6-fold lower than that for the same particles in water (at time scale τ = 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, Deff was 200-fold lower in mucus than in water. For uncoated particles 100-500 nm in diameter, Deff was 2,400- to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200- to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery.

Original languageEnglish (US)
Pages (from-to)1482-1487
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number5
DOIs
StatePublished - Jan 30 2007

Keywords

  • Drug delivery
  • Mucosal tissues
  • PEG
  • Particle tracking

ASJC Scopus subject areas

  • General

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