Avoiding a Sticky Situation: Bypassing the Mucus Barrier for Improved Local Drug Delivery

Hannah C Zierden; Aditya Josyula; Rachel L Shapiro; Henry T Hsueh; Justin Hanes; Laura M Ensign

doi:10.1016/j.molmed.2020.12.001

Avoiding a Sticky Situation: Bypassing the Mucus Barrier for Improved Local Drug Delivery

Trends Mol Med. 2021 May;27(5):436-450. doi: 10.1016/j.molmed.2020.12.001. Epub 2021 Jan 4.

Authors

Hannah C Zierden¹, Aditya Josyula¹, Rachel L Shapiro¹, Henry T Hsueh¹, Justin Hanes², Laura M Ensign³

Affiliations

¹ Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
³ Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287, USA; Departments Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: lensign@jhmi.edu.

Abstract

The efficacy of drugs administered by traditional routes is limited by numerous biological barriers that preclude reaching the intended site of action. Further, full body systemic exposure leads to dose-limiting, off-target side effects. Topical formulations may provide more efficacious drug and nucleic acid delivery for diseases and conditions affecting mucosal tissues, but the mucus protecting our epithelial surfaces is a formidable barrier. Here, we describe recent advances in mucus-penetrating approaches for drug and nucleic acid delivery to the ocular surface, the female reproductive tract, the gastrointestinal tract, and the airways.

Keywords: drug delivery; mucoadhesive; mucoinert; mucus; mucus penetrating; nanomedicine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Administration, Intravaginal
Administration, Ophthalmic
Administration, Topical*
Animals
Drug Administration Routes
Drug Delivery Systems / trends*
Epithelial Cells
Female
Gastrointestinal Tract
Humans
Mucous Membrane
Mucus*
Nanomedicine / methods
Nanoparticles* / chemistry
Nanoparticles* / therapeutic use

Abstract

Publication types

MeSH terms

Grants and funding