PFG‐NMR diffusometry: A tool for investigating the structure and dynamics of noncommercial purified pig gastric mucin in a wide range of concentrations

Abstract

For the first time, Pulsed Field Gradient-Nuclear Magnetic Resonance, a powerful noninvasive tool for studying the dynamics and structure of complex gels, has been used to measure diffusion of probe molecules in aqueous solutions/gels of noncommercial purified pig gastric mucin (PGM), in a concentration range up to 5 wt %. Complementary data were obtained from rheology measurements. The combination of techniques revealed a strong pH dependency of the structure of the PGM samples while changes in concentration, ionic strength, and temperature appeared to induce less pronounced alterations. Viscosity was found to vary in a nonmonotonous way with pH, with the more viscous solutions found at intermediate pH. We propose that this finding is due to a reduced charge density at lower pH, which is expected to continuously increase the relative importance of hydrophobic associations. The results suggest a loose network of expanded fully charged PGM molecules with considerable mobility at neutral pH (pH 7.4). At intermediate pH (pH 4), a three-dimensional expanded network is favored. At pH 1, the charge density is low and microphase separation occurs since hydrophobic associations prevail. This leads to the formation of clusters concentrated in PGM molecules separated by regions depleted in PGM. The results obtained increase our knowledge about the gastric mucosal layer, which in vivo contains mucin in the same concentration range as that of the samples investigated here.

Mathematical modeling of molecular diffusion through mucus

“…Using pulse-field NMR, Gibbs et al was able to confirm concentration-dependent diffusion of 19F-Ovalbumin through both solution and porous media[88]. Lafitte et al recently showed diffusion of ethanol and glucose through mucin gel, in a setup similar to top-down capillary tube one dimensional diffusion model[89, 90] This technology is limited, however, to solute or tracers with strong paramagnetic groups.…”

Methods to determine the interactions of micro- and nanoparticles with mucus

“…utilized the diffusion of poly(ethylene glycol) polymers (PEGs) spanning a molecular weight range 1020 g mol -1 < Mw < 716,500 g mol -1 through pig gastric mucin (PGM) (5 wt %) as a probe to understand the relative importance of pH, ionic strength and temperature on defining mucin gel structure [69]. They concluded that the structure of the mucin gel -as perceived by the stronger dependency on the PEG diffusion -was dominated by pH effects, compared with ionic strength and temperature effects.…”

Diffusion of Nutrients Molecules and Model Drug Carriers Through Mucin Layer Investigated by Magnetic Resonance Imaging with Chemical Shift Resolution

“…These observations show that ethanol molecules diffuse slower through the mucin gel than glucose molecules do. At pH 7.4, the mucin gel at 5 wt% consists of expanded molecules forming a network 10. Small molecules such as ethanol, may then be trapped more easily within this network than larger molecules.…”