Cell membrane Enhanced transport

Cell membranes are lipophilic and designed to be barriers against large anionic molecules, although there is a natural mechanism for intercellular transport of anionic oligonucleotides. In order to enhance membrane transport, antisense oligonucleotides are frequentiy modified by covalent attachment of carrier molecules or lipophilic groups. 

The transport behavior of Li+ across membranes has been the focus of numerous studies, the bulk of which have concentrated upon the human erythrocyte for which the Li+ transport pathways have been elucidated and are summarized below. The movement of Li+ across cell membranes is mediated by transport systems which normally transport other ions, therefore the normal intracellular and subcellular electrolyte balance is likely to be disturbed by this extra cation. Additionally, Li+ has been shown to increase membrane phospholipid unsaturation in rat brain, leading to enhanced fluidity in the membrane, which could have repercussions for membrane-associated proteins and for membrane transport properties. 

Some studies indicated that exogenous zearalenone influences plant growth and development. For example, zearalenone stimulated the initiation of the vegetative bud in tobacco pith callus tissue (Mirocha et al. 1968), inhibited the cell membrane transport of maize roots (Vianello and Macri 1981) and enhanced the a-amylase and P-glucosidase activities of germinating maize seeds. 

The mechanism by which Na" is reabsorbed in coupled exchange with and K+ in the collecting duct has been discussed previously that is, Na+-driven K+ secretion is partially under mineralocorticoid control. Aldosterone and other compounds with mineralocorticoid activity bind to a specific mineralocorticoid receptor in the cytoplasm of late distal tubule cells and of principal cells of the collecting ducts. This hormone-receptor complex is transported to the cell nucleus, where it induces synthesis of multiple proteins that are collectively called aldosterone-induced proteins. The precise mechanisms by which these proteins enhance Na+ transport are incompletely understood. However, the net effect is to increase Na" entry across apical cell membranes and to increase basolateral membrane Na+-K+-ATPase activity and synthesis. 

Receptor-mediated transporters are excipients that serve as substrates to exploit specific receptors present on cell membranes. Examples of various receptors that have been explored for permeation enhancement include bile acids (45), vitamin Bi2 (46), amino acids (47), and folic acid (48). Most of the work in receptor-mediated transporters is conducted via the use of prodrugs. For example, a prodrug of acyclovir conjugated to bile acids was seen to have higher permeability as compared to the original drug, because of receptor-mediated transport of the prodrug via bile acid transporters (49). 

Therefore, the enhancement of transport is not accompanied by damage to the cells, which is superior to the absorption-enhancing effects of other small molecules, which lead to irreversible changes in the cell membrane and damage to the cell. Thus, much attention has been paid to chitosan as a polymeric substance that enhances GI absorption. 

Due to their highly biocompatible nature, dendritic PGs have a broad range of potential applications in medicine and pharmacology. The versatility of the polyglycerol scaffolds for application in the biomedical field has recently been reviewed [131], and a number of examples were described, therein, e.g., smart and stimuli-responsive delivery and release of bioactive molecules, enhanced solubilization of hydrophobic compounds, surface-modification and regenerative therapy, as well as transport of active agents across biological barriers (cell-membranes, tumor tissue, etc.). 

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