The role of mucus on drug transport and its potential to affect therapeutic outcomes

Adv Drug Deliv Rev. 2018 Jan 15:124:82-97. doi: 10.1016/j.addr.2017.10.009. Epub 2017 Oct 26.

Abstract

A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation. The natural protective role of mucus is nowadays acknowledged as a major barrier to be overcome in non-invasive drug delivery. The heterogeneity of mucus components offers a wide range of potential chemical interaction sites for macromolecules, while the mesh-like architecture given to mucus by the intermolecular cross-linking of mucin molecules results in a dense network that physically, and in a size-dependent manner, hinders the diffusion of nanoparticles through mucus. Consequently, drug diffusion, epithelial absorption, drug bioavailability, and ultimately therapeutic outcomes of mucosal drug delivery can be attenuated.

Keywords: Hydrogel; Mucins; Mucoadhesion; Mucopenetration; Mucosal drug delivery; Nanoparticles; PEGylation; Rheology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Drug Delivery Systems
  • Humans
  • Mucus / chemistry
  • Mucus / metabolism*
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*

Substances

  • Pharmaceutical Preparations