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Nanomedicine (Lond). 2016 Jun;11(11):1337-43. doi: 10.2217/nnm-2016-0047. Epub 2016 May 12.

Nanoparticles coated with high molecular weight PEG penetrate mucus and provide uniform vaginal and colorectal distribution in vivo.

Maisel K1,2, Reddy M1,2, Xu Q1,3, Chattopadhyay S1,4, Cone R1,5, Ensign LM1,3,4, Hanes J1,2,3,4,6.

Author information

1
Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
2
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
3
Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.
4
Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
5
Department of Biophysics, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
6
Departments of Neurosurgery, Oncology, & Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, USA.

Abstract

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.

KEYWORDS:

PEG density; PEG molecular weight; hypotonic delivery; mucosal drug delivery; mucus penetrating nanoparticles (MPPs)

PMID:
27171816
PMCID:
PMC4897967
DOI:
10.2217/nnm-2016-0047
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Financial & competing interests disclosure This work was supported by NIH grants R33AI094519, R33AI079740, U19AI133127, the W. W. Smith Charitable Trust (A1302), the Johns Hopkins University Center for AIDS Research (P30AI094189), and the NSF graduate research fellowship program (K Maisel). The mucus penetrating particle technology is being developed by Kala Pharmaceuticals. J Hanes is a co-founder of Kala. J Hanes and R Cone own company stock, which is subject to certain restrictions under University policy. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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