Permeation cell

Kulkarni, A., Han, Y., and Hopfinger, A. J., Predicting Caco-2 cell permeation coefficients of organic molecules using membrane-interaction QSAR analysis, /. Chem. Inf. Comput. Sci., 2002, 42, 331-342. 

Ouyang, H., Tang, F., Siahaan, T. J., Borchardt, R. T., A modified coumarinic acid-based cyclic prodrag of an opioid peptide its enzymatic and chemical stability and cell permeation characteristics, Pharm. 

Platts JA, Abraham MH, Hersey A, Butina D (2000) Estimation of molecular linear free energy relationship descriptors. 4. Correlation and prediction of cell permeation. PharmRes 17 1013-1018. 

G. P. Camenisch, W. Wang, B. Wang, R. T. Borchardt, A Comparison of the Bioconversion Rates and the Caco-2 Cell Permeation Characteristics of Coumarin-Based Cyclic Prodrugs and Methylester-Based Linear Prodrugs of RGD Peptidomimetics , Pharm. Res. 1998, 15, 1174- 1181. 

Achieving cell permeation may, in him, reduce the free Fe(III) pool, shifting the cellular equilibrium Fe(II)/Fe(III) toward Fe(III), thereby reducing the level of Fe(II) free to participate in the Fenton reaction (see Section III). 

Predicting Caco-2 cell permeation coefficients of organic molecules using membrane-interaction QSAR analysis. 

Several papers have also been published in which a correlation has been sought between permeation across Caco-2 cells and physicochemical properties of the compounds. The review article by Ekins et al. (2000) discusses several studies to predict Caco-2 cell permeation. Correlations have been found with polar surface area, hydrogen bond descriptors, VolSurf, and other parameters. Van de Waterbeemd et al. (2001a) also discuss models for predicting oral absorption of compounds, including the use of Caco-2 cell lines. This paper also provides much useful information on the optimization of pharmacokinetic parameters in drug development. 

Fig. 6.6. Chemical modification of deoxyoligonucleotides aimed at increasing nuclease resistance and cell permeation.

LION Bioscience—providerof iDEA, a modular ADME predictive system. The absorption module predicts Caco-2 cell permeation, and performs dose-response modeling of the oral absorption. The metabolism module predicts first-pass effects and models metabolic parameters. Future modules are planned for distribution and elimination (124). 

Although the objective of most absorption enhancers is to avoid direct interaction with the mucosal membrane, cell permeation enhancers use this as a means to increase drug absorption. One form of enhancer currently of interest consists of glycosylated molecules, or facial amphiphiles. It is claimed that these compounds temporarily increase membrane permeability. Molecules are designed to self-assemble in membranes to form transient pores that permit hydrophilic com-poimds to cross the membrane. This technology has considerable potential for absorption enhancement. No adverse effects have been reported to date. ... 

Extent of Damage to Mucosal Cells. Permeation enhancement implies possible alteration of the protective permeability barrier either by 1) an increase in the fludity of intercellular lipids (relatively non-toxic) and/ or 2) extraction of intercellular lipids or denaturation of cellular proteins (much more damaging/toxic). Therefore, it is imperative that the permeation enhancer 1) exert a reversible effect 2) not be systemically absorbed and 3) not cause cumulative toxicity or permanent changes in the barrier properties. Application of up to 1% sodium lauryl sulfate or cetylpyridinium chloride to the ventral surface of the tongue of dogs resulted in desquamation, widening and separation of keratin.f The buccal mucosa of rabbits treated with... 

Cell permeation PGU C Cell permeation Perm coeff. P < 10 mfs" ... 

Galvez, A., Maqueda, M., Martinez-Bueno, M., Valdivia, E. (1991). Permeation of bacterial cells, permeation of C54oplasmic and artificial membrane vesicles, and channel formation on lipid bilayers by peptide antibiotic AS-48. Journal of Bacteriology, 173, 886-892. 

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