Cell membrane passage

The liposomal encapsulation technology is focused on cosmetic and pharmaceutical systems, since the PC fractions are quite costly. Plant scale produced PC phospholipids are used as excipients for targeted drugs transport, encapsulation and cell membrane passage. 

FIG. 22-58 Concentration profile of electrolyte across an operating ED cell. Ion passage through the membrane is much faster than in solution, so ions are enriched or depleted at the cell-solution interface, d is the concentration boundary layer. The cell gap, A should he small. The ion concentration in the membrane proper will he much higher than shown. (Couttesij Elsevier.)... 

Phospholipids are found widely in both plant and animal tissues and make up approximately 50% to 60% of cell membranes. Because they are like soaps in having a long, nonpolar hydrocarbon tail bound to a polar ionic head, phospholipids in the cell membrane organize into a lipid bilayer about 5.0 nm (50 A) thick. As shown in Figure 27.2, the nonpolar tails aggregate in the center of the bilayer in much the same way that soap tails aggregate in the center of a micelle. This bilayer serves as an effective barrier to the passage of water, ions, and other components into and out of cells. 

Figure 3.3 The passage of drugs across cell membranes.

Mammalian intestinal absorption requires the presence of two receptors and two transporters, which is itself a unique feature. Specific transporters such as intrinsic factor, transcobalamin, and haptocorrin have been characterized,1113 as well as a number of receptors for passage across cell membranes. A number of biochemical studies on cell uptake1114 and receptors1115,1116 of cobala-mins have been reported. Genetic disorders that impair the synthesis, transport, or transmembrane passage of cobalamins and their consequences have been reviewed.1117,1118... 

To reach such a site, a molecule must permeate through many road blocks formed by cell membranes. These are composed of phospholipid bilayers - oily barriers that greatly attenuate the passage of charged or highly polar molecules. Often, cultured cells, such as Caco-2 or Madin-Darby canine kidney (MDCK) cells [1-4], are used for this purpose, but the tests are costly. Other types of permeability measurements based on artificial membranes have been considered, the aim being to improve efficiency and lowering costs. One such approach, PAMPA, has been described by Kansy et al. [5],... 

When a wave of excitation starts at a specified point on the fibre this potential difference is abolished and reversed and the surface becomes electronegative with regard to the unexcited portions of the fibre (fig. 16). ( Depolarization coincides with a ohange in the surface of the membrane of the cell which first allows Na+ ions from the tissue fluids to pass into the cell and K+ ions to pass outwards. In the undisturbed state, the cell membrane is relatively impermeable to the Na+ ions which are kept outside and the concentration of K+ ions inside the cell is greater than in the external fluids.) This induced negativity at the excited spot causes local electrical circuits to arise and so new points of excitation are caused (Fig. lc). The passage of electrical disturbance is shown in both directions. In the body, however, the fibres are stimulated at only one end, and hence induction is in one direction. 

In reality, there is more than just passive diffusion at work for drugs to traverse the cell membrane. Most drugs are absorbed in the intestine. Often, if an oral drug is taken and a fast response is desired, the drug is taken on an empty stomach to ensure a quick passage through the stomach for absorption in the intestine to take place. 

Cross section of lightweight fuel cell membrane electrode assembly having integral reactant flow passages. (From J. P. Wilkinson et al. (1999) U.S. Patent 5976726.)... 

The process of transcytosis is illustrated in Figure 2.3 for the transferrin receptor (TfR) [37]. The receptor is heavily expressed at the BBB compared to other vascular beds [38]. Transferrin or a monoclonal antibody to the extracellular domain of the receptor protein will bind from the luminal side of the BBB. This triggers cellular uptake by the mechanism of receptor-mediated endocytosis, i.e. the invagination and budding off of parts of the cell membrane as a result of the formation of small vesicles (endosomes). The transceUular passage of ligand (transcytosis) is completed by exocytosis at the abluminal membrane, and the whole process is completed within minutes in vivo. 

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. 

Compounds can cross biological membranes by two passive processes, transcellu-lar and paracellular mechanisms. For transcellular diffusion two potential mechanisms exist. The compound can distribute into the lipid core of the membrane and diffuse within the membrane to the basolateral side. Alternatively, the solute may diffuse across the apical cell membrane and enter the cytoplasm before exiting across the basolateral membrane. Because both processes involve diffusion through the lipid core of the membrane the physicochemistry of the compound is important. Paracellular absorption involves the passage of the compound through the aqueous-filled pores. Clearly in principle many compounds can be absorbed by this route but the process is invariably slower than the transcellular route (surface area of pores versus surface area of the membrane) and is very dependent on molecular size due to the finite dimensions of the aqueous pores. 

Significant interlaboratory differences in permeability measurements are observed with cell-based assays. It is important to standardize culture conditions and characterize a cell line within one s own laboratory. Permeability differences can be attributed to a number of factors, for example, heterogenecity of cell line, passage number, culture conditions, characteristics of the filter membrane, age of mono-layers and level of differentiation and experimental methodology used. Active... 

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