Abstract
Mucus covers the epithelium found in all intestinal tracts, where it serves as an important protecting barrier, and pharmaceutical drugs administrated by the oral, rectal, vaginal, ocular, or nasal route need to penetrate the mucus in order to reach their targets. Furthermore, the diffusion in mucus as well as the viscosity of mucus in the eyes, nose and throat can change depending on the relative humidity of the surrounding air. In this study we have investigated how diffusion through gels of mucin, the main protein in mucus, is affected by changes in ambient relative humidity (i.e. water activity). Already a small decrease in water activity was found to give rise to a significant decrease in penetration rate through the mucin gel of the antibacterial drug metronidazole. We also show that a decrease in water activity leads to decreased diffusion rate in the mucin gel for the fluorophore fluorescein. This study shows that it is possible to alter transport rates of molecules through mucus by changing the water activity in the gel. It furthermore illustrates the importance of considering effects of the water activity in the mucosa during development of potential pharmaceuticals.
Highlights
Mucus gels exist on the luminal surface of the gastrointestinal, urogenital and respiratory tract as well as on the cornea of the eye
We have investigated how the diffusion coefficient of fluorescein varies with the water activity in mucin gels using fluorescence recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS) measurements
Assuming that water penetration through the silicone membrane is small compared to water penetration through the Millipore GV0.22 filter, the water activity in the mucin gels is regulated by the water activity in the donor compartment
Summary
Mucus gels exist on the luminal surface of the gastrointestinal, urogenital and respiratory tract as well as on the cornea of the eye. The major protein family in mucus, is responsible for the gel forming properties of mucus [1,2,5]. These large glycoproteins display a vast polydispersity in both mass and size [1] and can assemble into long chains [6,7,8], bridged together by disulfide bonds. Entanglement of these long mucin chains is considered to be the primary mechanism for gel formation [1,6]. Rheology measurements have shown that the viscoelastic properties of mucin are largely dependent on the mucin
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