Nanoparticles Coated with High Molecular Weight PEG Penetrate Mucus and Provide Uniform Vaginal and Colorectal Distribution in Vivo
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AIM: We previously reported that nanoparticles (NPs) coated with 10 kDa PEG were mucoadhesive. Here, we demonstrate that by increasing the surface density, PEG with molecular weight (MW) as high as 40 kDa can be used as a mucoinert NP surface coating. MATERIALS & METHODS: We compared two sets of reaction conditions for coating model polystyrene NPs with 10 kDa PEG and used optimized conditions to coat NPs with PEG as high as 40 kDa in MW. We then characterized NP transport in human cervicovaginal mucus ex vivo. We further administered PEG-coated NPs to the mouse cervicovaginal tract and colorectum to assess mucosal distribution in vivo. RESULTS & CONCLUSION: We demonstrate here that PEG with MW as high as 40 kDa can be densely grafted to the surface of NP to prevent interactions with mucus. NP coated with 10-40 kDa PEG rapidly diffused through human cervicovaginal mucus ex vivo, and uniformly lined the mouse colorectal and vaginal epithelium in vivo.
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PEG can confer mucus-penetrating properties due to its polarity and net neutral charge, enhancing nanomedicine penetration through mucosal barriers.
“These mucus penetrating properties are conferred by the polarity of the molecule and overall net neutral charge which has been shown to enhance the penetration of nanomedicines through mucosal barriers [72, 73].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [73]
The Background says the authors hypothesized that PEG’s hydrophilic, uncharged nature could prevent mucoadhesion, and reports rapid diffusion of densely PEG-coated nanoparticles through mucus. But it qualifies this effect: sufficient coating density is needed, and the proposed mechanism is a hypothesis rather than an established consequence of polarity and charge alone. No page number is available in our copy. (LLM, conf=0.87)
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References 31 · Cited by 147
- Authors
- Maisel, K., Reddy, M., Xu, Q., Chattopadhyay, S., Cone, R., Ensign, L. M., & Hanes, J.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Ensign, Laura M
- Hanes, Justin
- Venue
- Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2016-05-12
- Volume
- 11
- Issue
- 11
- Pages
- 1337-1343
- ISSN
- 1743-5889 (ISSN-L)
- 1748-6963
- PMC
- PMC4897967
- OpenAlex
- W2349620323
- Cited by
- 147
- References
- 31
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 12 · 2023: 18 · 2022: 15 · 2021: 17 · 2020: 19 · 2019: 16 · 2018: 13 · 2017: 11 · 2016: 1
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nanomedicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R33AI094519, R33AI079740, U19AI133127)
- The W. W. Smith Charitable Trust (A1302)
- The Johns Hopkins University Center for AIDS Research (P30AI094189)
- The NSF graduate research fellowship program (P30AI094189)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- PEG-coated nanoparticles, mucoadhesion, mucus penetration, cervicovaginal mucus, vaginal drug delivery, nanoparticle coating, polystyrene nanoparticles
- MeSH terms
- Animals, Cervix Mucus, Cervix Uteri, Colon, Drug Carriers, Female, Humans, Molecular Weight, Mucus, Polyethylene Glycols, Polystyrenes, Rectum, Tissue Distribution, Vagina, Mice, Nanoparticles
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