Cellular efflux system

FIGURE 28.4 Schematic illustration twofold effects of Pluronic block copolymer on Pgp drug efflux system. Inhibition of Pgp activity is due to a combination of two cellular pathways depletion of ATP levels and membrane fluidization in the cells. 

MDTs provide a survival strategy for living organisms that are constantly assailed by a host of harmful chemicals from the environment. Because of the diversity of these xenobiotics , cellular survival mechanisms must deal with an immense variety of molecules. MDTs supply one such strategy. The patterns of abundance of drug efflux systems in different organisms do... 

Figure 47.3. Schematic illustrating twofold effects of Pluronic block copolymers with intermediate lipophilicity on Pgp and MRPs drug efflux system. These effects include (a) decrease in membrane viscosity ( fluidization ) resulting in inhibition of Pgp and MRPs ATPase activity, and (b) ATP depletion in BMVEC. Extremely lipophilic or hydrophilic Pluronic block copolymers do not cross the cellular membranes and do not cause energy depletion in the cells.

Dmg loading in micro- and nanoparticulate systems is generally carried out by one of two methods, i.e. during the preparation of particles (incorporation) or after their formation (incubation). The dmg delivery properties are also essentially dependent on the chemical and textural properties of the matrices, the porosity, wettability, erosion and the surface area. The matrix equally has an impact on the discharge profile for the bioavailability of the entrapped dmg. Nanoparticle-based delivery systems have the potential power to improve dmg stability, increase the duration of the therapeutic effect and permit enteral or parenteral administration, which may prevent or minimize dmg degradation and metabolism as well as cellular efflux [70, 71]. Protein nanoparticles can conveyance medications transversely across the blood-brain barrier that are not usually passed across after injection. A number of authors have demonstrated a considerable tendency for an accumulation of protein nanoparticles in certain tumours. The binding of a variety of cytotoxic dmgs, such as 5-fluorouracil,... 

While our data using this technique are still preliminary, we have observed that 25 yU/ml insulin inhibits the rate of calcium efflux from renal slices (28). This effect of insulin was gradually reduced at the higher concentrations of insulin. The effects of insulin on calcium exchange appear to be localized in the mitochondrial compartment. Further work is needed to determine whether insulin affects specific enzyme systems which are known to play a role in renal calcium transport, and which cellular or subcellular compartments are involved. This would substantially increase our understanding of the regulation of urinary calcium excretion, and of ways in which excessive loss of calcium by this route might be avoided. 

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