Membrane passage

In this chapter we address several phenomena involving a solvent, principally water, and a stationary surface. These include various wetting and wall effects, chromatography, and membrane passage. Some of these phenomena have been modeled with cellular automata, and a brief description of those studies will be presented. Each of these examples opens up a wealth of possibilities for future work, and the reader is urged to pursue some studies that these may inspire. 

Example 6.7. Membrane passage as a function of solute hydropathic state... 

An alternative method which could be used to establish the fraction of protein that actually reaches the alveoli is the so-called co-aerosohzation. If a protein is aerosolized from a solution that also contains another low molecular weight substance (deposition marker), it can be assumed that the fractions of protein and deposition marker reaching the alveoli will be the same. The deposition marker should be a substance with a known alveolar epithelial membrane passage (e.g. tobramycin or a decapeptide) which does not undergo absorption after oral administration. The fraction of the deposition marker that is deposited in the alveoli can be established from plasma (and urine) measurements of the deposition marker. The maximum fraction of protein that can pass the alveolar membrane whl then be known. The ratio between the deposited fraction and the fraction that has been absorbed into the systemic circulation (as can be estabhshed form plasma or urine analysis) will provide an estimation of the protein passage across the alveolar membrane. 

Alternatively the membrane passage of human airway epithehal ceh lines can be studied in vitro. A number of bronchial epithehal ceh hnes is available, such as the 16HBE14o- and Calu-3 cell hnes. These ceh hnes can be installed in diffusion chambers to measure transport rates [34]. A major disadvantage of the currently used cell hnes is that they provide information about bronchial epithehal transport only. Since bronchial epithelium is very different from alveolar epithehum, the information from these in vitro studies is of limited value for the prediction of the bioavahabihty of pulmonary administered proteins. 

Drug stability and absorption are also affected by its compatibility towards vaginal fluids (especially for pH, enzymes, and microflora) and vaginal membrane passage [5],... 

There is hindered membrane passage of large molecules. 

Except for direct membrane passage by protein transduction domains (see section below), payload internalized via endocytic pathways still remains entrapped within intracellular vesicle. However, most therapeutically active... 

Figure 19. Bacterial representatives of active ion-transport through membranes, modeling phase-transition strategies of protein information function lines stereo-presentation of a CPK-valinomycin movie , mediating by highly sophisticated biomesogenic interplays a K -ion membrane passage [7 a, 33 p, q, 35].

Deviations may occur for substances of large molecular diameter due to hindered membrane passage. Lack of permeation was observed for chemicals with effective cross sections > 9.5 A (Opperhuizen et al., 1985). It was... 

Passive transport of lipophilic substances may occur via the fluid bilayer membrane of the cells lining the membranes. This transcellular route is the most important route for membrane passage of active substances. This transport mechanism is not only driven by the concentration gradient over the absorptive membrane, but also by the oil to water partition coefficient of the active substance (expressed as the octanol-water partition coefficient, which describes the ratio of the substance s solubility in aqueous and fatty phases, see Sect. 16.1.9). More lipophilic... 

The bioavailability of an active substance is defined as the fraction of the active substance that reaches the systemic circulation intact. It equals the pharmaceutical availability in vivo, minus the loss of the active substance during the absorption into the systemic circulation, due to incomplete membrane passage or loss caused by metabolism of the active substance during the absorption process. 

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