Gastrointestinal tract epithelium

CCAs of tissues such as the skin, the gastrointestinal tract epithelium, and the lung epithelium are... 

Delivery of peptides and proteins via the gastrointestinal tract has not been successful because of poor penetration through the intestinal epithelium and high levels of proteolytic activity in the gastrointestinal tract. Liposomal encapsulation of proteins and peptides will not improve the efficiency and capacity of this absorption pathway considerably (e.g., Ryman et al., 1982 Machy and Leserman, 1987 Weiner and Chia-Ming Chiang, 1988). These difficulties in delivery via the oral route caused the parenteral route to remain the preferred route for the administration of therapeutic peptides... 

Figure 4.2 Substructure of the wall in the gastrointestinal tract. (Not to scale). Epithelial cells of the villi possess micro villi which extend into the lumen (Not shown). The epithelium consists of absorptive enterocytes, endocrine cells that secrete peptide and goblet cells that secrete mucus.

For some substances, a wealth of genotoxicity data may be available from studies conducted in vitro and/or in vivo. In addition to studies conducted according to test guidehne methods, there may be nonstandard studies available in which first site of contact tissues, i.e., skin, epithelium of the respiratory or gastrointestinal tract, have been examined. In addition, data from plant, fungal, or insect Drosophila) systems may be available. Occasionally, studies of genotoxic effects in humans may also be available. The vahdity and usefulness of each of the data sets to the overall assessment... 

Vitamin A deficiency is worldwide one of the most prevalent nutrition-dependent deficiency diseases. It leads to changes of the respiratory epithelium, which result in repeated infections of the respiratory tract, the main cause of death in vitamin A-deficient children. The difficulty in supplying the respiratory epithelium with vitamin A is that the affected children frequently suffer as well from infections of the gastrointestinal tract with subsequent reduction of the absorption of fat-soluble vitamins. Nutritargeting can in these cases avoid the problems of malabsorption and ensure the micronutrient supply. 

The major limitation to developing therapeutic proteins in nonparenteral dosage forms is the poor permeability of these water-soluble and hygroscopic macromolecules across the tissue layers at the site of drug administration. These tissue layers include the epithelium of the gastrointestinal tract, the stratum corneum of the skin, and the epithelium lining of the alveoli and nasal cavity. 

In this equation, FB is defined as the bioaccessibility coefficient, z. e., fraction of lipid released from the food matrix into juices of the gastrointestinal tract FT is defined as the transport coefficient, i.e., fraction of the released lipid component transported across the intestinal epithelium and Fm is the fraction of the lipid component that reaches the systemic circulation without being metabolized. It is usually important to measure the concentration of a bioactive component at a particular location to establish its efficacy. Thus, the concentration-time profile of a specific bioactive component at a particular site of action may be helpful in the... 

It has been shown that antibodies can reach the systemic circulation after oral administration, but only to a very small extent. The antibodies pass the intestinal epithelium not by passive transcellular but by receptor-mediated transcellular or paracellular transport. The Fc part of the antibody is responsible for the saturable receptor-mediated transport, especially IgG in breast-fed neonates. As the receptor is found primarily in the gastrointestinal tract of neonates, it was called Fc-Rn (Fc receptor neonatal). Apart from this location, Fc-Rn has also been discovered in other tissues such as the liver. Its role will be further discussed in Section 3.9.3. 

Penetration enhancers are substances that can increase the absorption of a co-administered dmg, and include surfactants, bile salts, chelating agents, and fatty acids. Penetration enhancers are widely used in dmg delivery to potentiate absorption across various types of epithelia, including the epithelium of the gastrointestinal tract. However, a major limiting factor in the general acceptance of absorption enhancers for improving oral dmg absorption is the non-specific nature of their effects. 

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