Membranes with barriers

Besides the work with Carr and Schmidt, I had a very pleasant interaction with Ed Cussler over some problems in mass transfer through membranes with barriers [238], through anisotropic membranes [232], and by facilitated diffusion [247]. A severely mathematical problem of diffusion through a slot could be solved by a Schwartz-Christoffel transformation,41 and provided an asymptotic formula that proved useful in the barrier problem [223]. Cussler was delightful to work with because he refused to accept any mathematical solution that could not be unpacked and shown to be physically sensible (cf. [244]). Next to Bosanquet, he is the most intuitive problem solver with whom I have worked. Chapter 19 [232] is reprinted here. 

The thylakoid membrane is asymmetrically organized, or sided, like the mitochondrial membrane. It also shares the property of being a barrier to the passive diffusion of H ions. Photosynthetic electron transport thus establishes an electrochemical gradient, or proton-motive force, across the thylakoid membrane with the interior, or lumen, side accumulating H ions relative to the stroma of the chloroplast. Like oxidative phosphorylation, the mechanism of photophosphorylation is chemiosmotic. 

All these attempts to improve the membrane characteristics by decreasing the methanol crossover and increasing their temperature resistance gave encouraging results. However, modification of the existing membranes (e.g., with barrier screens) without decreasing the electrical... 

Using liposomes made from phospholipids as models of membrane barriers, Chakrabarti and Deamer [417] characterized the permeabilities of several amino acids and simple ions. Phosphate, sodium and potassium ions displayed effective permeabilities 0.1-1.0 x 10 12 cm/s. Hydrophilic amino acids permeated membranes with coefficients 5.1-5.7 x 10 12 cm/s. More lipophilic amino acids indicated values of 250 -10 x 10-12 cm/s. The investigators proposed that the extremely low permeability rates observed for the polar molecules must be controlled by bilayer fluctuations and transient defects, rather than normal partitioning behavior and Born energy barriers. More recently, similar magnitude values of permeabilities were measured for a series of enkephalin peptides [418]. 

In the example above, the solutions are assumed to be well stirred and mixed the aqueous resistance is negligible, and the membrane is the only transport barrier. However, in any real case, the solutions on both sides of the membrane become less and less stirred as they approach the surface of the membrane. The aqueous diffusion resistance, therefore, very often needs to be considered. For example, for very highly permeable drugs, the resistance to absorption from the gastrointestinal tract is mainly aqueous diffusion. In the section, we give a general solution to steady diffusion across a membrane with aqueous diffusion resistance [5],... 

Recently in our group, model membrane permeation barriers have been constructed with concentrated phospholipid solutions, 10-74% wt/vol soy lecithin (approximate %w/w lipid composition 24% PC, 18% PE, 12% PI cf. Table 3.1) in dodecane, supported on high-porosity, hydrophobic microfilters. This newly formulated lipid has a net negative charge at pH 7.4, which further increases above pH 8, as the ethanolamine groups deionize. Also tested were 10% wt/vol egg lecithin lipid solutions in dodecane (approximate composition 73% PC, 11% PE,... 

Due to these practical aims, membranes with low oxygen permeability have been developed. Some of them are PVA, PVA blends or their derivative membranes, due to the PVA excellent oxygen barrier properties [18],... 

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

Lipid solubility determines the readiness of drug molecules to cross the gastrointestinal tract, blood-brain barrier, and other tissues. Molecular size is another factor that determines the diffusion of drugs across the membrane, with the smaller molecules able to diffuse more readily. Exhibit 5.2 describes the kinetics for diffusion of drug molecules across the cell membrane. 

Falten et al. recently reported that phospholipid membrane vesicles can be con-stmcted on a filter scaffold without any organic solvent [57-60]. In this system, the phospholipid vesicle occupies the filter pores to form a permeation barrier. This is more relevant to the cellular membrane than PAMPA membranes with organic solvent. The membrane can be stored up to two weeks without significant change and is stable at pH 2-8. The Fa% predictability was compared with BM-PAMPA, DS-PAMPA, Caco-2 and immobilized liposome chromatography, resulting in promising predictability. 

Results of this study confirm the expected improved recoveries of trace organics with membranes more selective and more highly cross-linked than the classical cellulose acetate membrane. Improved recoveries were predicted from literature data reported for similar membrane types. In light of these results, cellulose acetate should no longer be considered for applications such as these. Further improvements in recovery can be expected as developmental membranes with more highly selective barriers are brought into commercial use. Each new membrane type considered for use on disinfected waters should be evaluated for sensitivity to common disinfectants (oxidants). Both decreased selectivity and potentially troublesome chemical breakdown products should be considerations under these conditions. Although the cellulose acetate and FT-30 composite membranes did not prove to be particularly sensitive to chlorine, many commercially available... 

If skin is placed in a water bath under controlled conditions [14] the primary barrier to transdermal delivery, the epidermal membrane comprising the stratum corneum and viable epidermis, can be readily removed and used to analyze the penetration and diffusion of materials. Figure 18.3a and Figure 18.3b show the appearance of human breast epidermal membrane, with epidermis facing uppermost, following application of the cylindrical dry-etch and pyramidal wet-etch silicon microneedles, respectively. In each case the microneedles are clearly shown to pierce the stratum corneum and viable epidermis to facilitate controlled access of molecules to the target region of skin. 

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