Mucus diffusion through

My assumptions were unrealistic, but Norman Heatley had already shown that mucus is no barrier to diffusion of acid. Heatley mixed thick hog mucus with brom-cresol green and drew it into a set of capillary tubes. Other tubes were filled with sodium bicarbonate solution at the same concentration prevailing in the mucus. All tubes were inserted vertically in wax at the bottom of a beaker, and the beaker was filled over the tips of the tubes with 0.2 N HCl. The distance acid traveled into the tubes was shown by the sharp blue-yellow boundary in the indicator dye. Heatley found the distance traveled to be roughly proportional to the square root of the time of diffusion, and there was no difference in diffusion between the bicarbonate tubes and tubes containing dilute mucus. Diffusion through concentrated mucus was very slightly slower. ... 

Just as aspirin continues to provide the same benefits as a century ago, it also produces some of the same problems. The major problem with aspirin is that it can upset the stomach. In the acidic environment of the stomach, aspirin can diffuse through the protective mucus lining and rupture cells and produce bleeding. Under normal doses, the amount of blood loss in most individuals is only a milliliter or two, but in some individuals who take heavy doses, gastrointestinal bleeding can be severe. To counteract this side effect, manufacturers include an antacid such as aluminum hydroxide and call the aspirin a buffered aspirin. This term is misleading because the antacid does not buffer the solution rather, it neutralizes some of the acidic effects of the aspirin. Another type of aspirin, called enteric aspirin, dissolves in the intestines where the environment is more basic. 

Interestingly, the use of mucolytic drugs, which alter the viscoelasticity of mucus, has been shown to increase the absorption of intranasally administered human growth hormone (22 kDa). In contrast, other studies have shown that antibodies (150-970 kDa) are able to diffuse through cervical mucus relatively unimpeded, a finding that suggests that the diffusion barrier to antibodies presented by mucus in the nasal cavity might be relatively minor [12]. 

Mucus serves as a lubricant and protective layer. Its most important property is its viscoelasticity, which enables it to act as a mechanical barrier, but also allows it to flow. The presence of a mucus layer has important implications for drag delivery. Mucus acts as a physical barrier through which drug molecules must diffuse, prior to reaching the absorbing surface. The rate of diffusion through the mucus will be dependent upon such factors as the thickness of the mucus layer, mucus viscosity and any interactions which may occur between the drag and mucus. 

Once in solution, the drug will diffuse through the mucus layer and enter the aqueous environment of the epithelial lining fluid. The rate of diffusion through the mucus will be dependent upon such factors as ... 

If the translocation of particles through mucus were only a function of particle size, virus-sized latex particles (< 100 nm) would diffuse through mucus readily (OmucuJDpbs 1, where D is diffusivity) (Fig. 4). However, latex particles adhere strongly to mucin fibers via hydrophobic interactions, resulting... 

Bhat PG, Flanagan DR, Donovan MD. Drug diffusion through cystic fibrotic mucus steady-state permeation, rheologic properties, and glycoprotein morphology. J Pharm Sci 1996, 85, 624-630. 

If volatile molecules have to diffuse through a layer of mucus that is at least 10 pm thick before reaching the neuron, molecular diffusion implies a temporal resolution no less than 0.1 second. In other words, fluctuations of odorant concentrations will not be detectable if they occur on a time scale much less than 0.1 second. This conclusion derives from the value of the diffusion constant for small molecules in solution (about 0.001 mm per second), which shows little dependence upon the identity of the solvent... 

To these species the structure of air currents is not invisible. A considerable portion of their brains has evolved to process information from their whiskers (or vibrissae), and one may plausibly suggest that their olfactory sensitivity derives, at least in part, from the ability to monitor the structure of air and to situate a scent within the currents that eddy about their snouts (Cain, et al., 1985). If, even in the absence of vibrissae, human olfaction can, nevertheless, sense the heterogeneity of odors, this adds another complexity to our experience of smell. As argued above, diffusion through mucus limits the temporal resolution of olfaction to about 0.1 second. If humans have the capacity... 

Figure 4.17 Reduced diffusion coefficient as a function of molecular size. Hydrodynamic radii were determined from the diffusion coefficient in water according to Equation 4-4. (a) Diffusion of proteins and peptides in mid-cycle human cervical mucus [5], Measurements were performed by FPR (squares) or quantitative imaging of fluorescence profiles (circles), (b) Protein and dextran diffusion through granulation (squares) or tumor tissue (circles) in the rabbit ear [20, 21]. (c) Glucose diffusion through capsular tissue (squares) and cartilage (circles and triangles) [92]. Each symbol represents a separate measurement.

Cu, Y. Saltzman, W. M. 2009. Mathematical modeling of molecular diffusion through mucus. Advanced Drug Delivery Reviews, 61, 101. 

However, as phosgene is relatively hydrophobic with low solubility in aqueous environments, it may not readily diffuse through the mucus and... 

Because the mucus layer or the underlying cells may serve as either final accumulation sites of toxic gases or layers through which the gases diffuse en route to the blood, we need simplified models of these layers. Altshuler et al. have developed for these layers the only available model that can be used in a comprehensive system for calculating tissue doses of inhaled irritants. It assumes that the basement membrane of the tracheobronchial region is covered with three discrete layers an inner layer of variable thickness that contains the basal, goblet, and ciliated cells a 7-Mm middle layer composed of waterlike or serous fluid and a 7-Mm outer layer of viscous mucus. Recent work by E. S. Boatman and D. Luchtel (personal communication) in rabbits supports the concept of a continuous fluid layer however, airways smaller than 1 mm in diameter do not show separate mucus and serous-fluid layers. 

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