title: Nanoparticles coated with high molecular weight PEG penetrate mucus and provide uniform vaginal and colorectal distribution in vivo.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Katharina
authors.initials: K
authors.lastname: Maisel
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Mihika
authors.initials: M
authors.lastname: Reddy
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Sumon
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Biophysics, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Cone
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.|Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Ensign
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.|Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.|Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.|Departments of Neurosurgery, Oncology, & Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
mesh_terms: D000818:Animals; D002582:Cervix Mucus / Q000378:metabolism; D002584:Cervix Uteri / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D009093:Mucus / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D012007:Rectum / Q000378:metabolism*; D014018:Tissue Distribution; D014621:Vagina / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D011137:Polystyrenes; D011092:Polyethylene Glycols
keywords: PEG density; PEG molecular weight; hypotonic delivery; mucosal drug delivery; mucus penetrating nanoparticles (MPPs)