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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.

The solution structure of the phosphocholine (PC) head group in 1,2-dipropionyl-sn-glycero-3-phosphocholine (C(3)-PC) in 30 mol. % dimethylsulfoxide (DMSO)-water solutions has been determined by using neutron diffraction enhanced with isotopic substitution in combination with computer simulation techniques. By investigating the atomic scale hydration structure around the PC head group, a unique description of the displacement of water molecules by DMSO molecules is detailed around various locations of the head group. Specifically, DMSO molecules were found to be the most prevalent around the onium portion of the head group, with the dipoles of the DMSO molecules being aligned where the negatively charged oxygen can interact strongly with the positively charged lipid group. The phosphate group is also partially dehydrated by the presence of the DMSO molecules. However, around this group the bulkier positive end of the DMSO dipole is interacting with negatively charged groups of the lipid head group, the DMSO layer shows no obvious ordering as it cannot form hydrogen bonds with the oxygen atoms in the PO(4) group such as water molecules can. Interestingly, DMSO-water contacts have also increased in the presence of the lipid molecule relative to DMSO-water contacts observed in pure DMSO/water solutions at similar concentrations., (© 2011 American Institute of Physics)

Abstract: Molecular dynamics simulations are used to provide a detailed investigation of the hydrogen bond networks around the phosphatidylcholine (PC) head group in 1,2-dipropionyl-sn-glycero-3-phosphocholine in pure water, 10mol.% and 30mol.% dimethylsulfoxide (DMSO)-water solutions. Specifically, it is observed that DMSO replaces those water molecules that are within the first solvation shell of the choline, phosphate and ester groups of the PC head group, but are not hydrogen-bonded to the group. The effect of the presence of DMSO on the hydrogen bond network around the PC head groups of the lipid changes with the concentration of DMSO. In comparison to the hydrogen bond network observed in the pure water system, the number of hydrogen-bonded chains of solvent molecules increases slightly for the 10mol.% DMSO system, while, in the 30mol.% DMSO system, the number of hydrogen-bonded chains of solvent molecules decreases. [Copyright &y& Elsevier]