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Cited by 1,050Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryInhalation and Respiratory Drug Delivery

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

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Lai, Samuel K., O'Hanlon, D. Elizabeth, Harrold, Suzanne, Man, Stan T., Wang, Ying-Ying, Cone, Richard, Hanes, Justin·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0608611104PMC PMC1785284
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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 ( D eff ) 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, D eff was 200-fold lower in mucus than in water. For uncoated particles 100–500 nm in diameter, D eff 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.

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  • Improved tissue uptake of PEGylated nanoparticles may be attributed to their higher diffusivity through the mucous layer.

    “Improved tissue uptake of PEGylated nanoparticles may be attributed to their higher diffusivity through the mucous layer-an observation shown using multiple particle tracking experiments by the Hanes lab 24 .”

    From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [24]

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Authors
Lai, S. K., O'Hanlon, D. E., Harrold, S., Man, S. T., Wang, Y.-Y., Cone, R., & Hanes, J.
Affiliations
  • Johns Hopkins University (US)
  • Biophysics and
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-01-30
Volume
104
Issue
5
Pages
1482-1487
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0608611104
PMC
PMC1785284
OpenAlex
W2102002215
Cited by
1,050
References
63
Citations by year
2026: 50 · 2025: 48 · 2024: 53 · 2023: 52 · 2022: 53 · 2021: 56 · 2020: 78 · 2019: 71 · 2018: 60 · 2017: 68 · 2016: 75 · 2015: 73 · 2014: 66 · 2013: 51 · 2012: 47
FWCI
23.33
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Johns Hopkins University
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Keywords
polymeric nanoparticles, mucus transport, cervicovaginal mucus, diffusion coefficient, particle size effects, polyethylene glycol coating, mucin, mucus viscoelasticity, particle immobilization, mucosal drug delivery, multiple particle tracking
MeSH terms
Biological Transport, Cervix Mucus, Diffusion, Drug Carriers, Female, Humans, Mucus, Particle Size, Polyethylene Glycols, Polymers, Time Factors, Water, Drug Delivery Systems, Nanoparticles

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