Epithelia permeability

Gorodeski GI [2000] cGMP-dependent ADP-depolymerization of actin mediates estrogen increase in human cervical epithelia permeability. Am J Physiol 279 C2028-C2036... 

Hidalgo IJ, Raub TJ, Borchardt RT (1989) Characterization of the human colon carcinoma cell line (CACO-2) as a model system for intestinal epithelia permeability. Gastroenterology 96 736-749... 

Di Colo, G., Zambito, Y., Zaino, C. Polymeric enhancers of mucosal epithelia permeability synthesis, transepitheUar penetration-enhancing properties, mechanism of action, safety... 

Nielsen HM, Verhoef JC, Ponec M, Rassing MR (1999b) TR146 cells grown on filters as a model of human buccal epithelium Permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate. J Control Release 60 223-233... 

Mucosa/Tissue Entire Epithelium Permeability Barrier Water Florseradish Peroxidase... 

Vaginal Rings. Vaginal epithelium is readily permeable to contraceptive steroids. Since the vascular drainage of the vagina bypasses the Hver, this route of adrninistration potentially permits utilisation of dmgs that have low oral activity. 

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride (CF) channel characterised by chloride permeability and secretion, and also by the regulation of other epithelial ion channels (Eidelman et al, 2001). Mutations in the CFTR gene lead to an impaired or absent Cl conductance in the epithelial apical membrane, which leads to defective Cl secretion and absorption across the epithelium. Genistein (Illek et al, 1995 Weinreich et al, 1997) and other flavonoids (Illek and Fisher, 1998) have been shown, in different animal and tissue models, to activate wild-type CFTR and CFTR mutants by (Eidelman et al, 2001 Roomans, 2001 Suaud et al, 2002) ... 

One of the key parameters for correlating molecular structure and chemical properties with bioavailability has been transcorneal flux or, alternatively, the corneal permeability coefficient. The epithelium has been modeled as a lipid barrier (possibly with a limited number of aqueous pores that, for this physical model, serve as the equivalent of the extracellular space in a more physiological description) and the stroma as an aqueous barrier (Fig. 11). The endothelium is very thin and porous compared with the epithelium [189] and often has been ignored in the analysis, although mathematically it can be included as part of the lipid barrier. Diffusion through bilayer membranes of various structures has been modeled for some time [202] and adapted to ophthalmic applications more recently [203,204]. For a series of molecules of similar size, it was shown that the permeability increases with octa-nol/water distribution (or partition) coefficient until a plateau is reached. Modeling of this type of data has led to the earlier statement that drugs need to be both... 

The permeability coefficient Kpcr is just the flux divided by Cw. It is apparent that the permeability coefficient is linear with P for small distribution coefficients and constant for large P. Thus, for small P the epithelium is the barrier, and for large P the stroma is the barrier. A fit for steroid permeability is shown in Fig. 12, where the regression analysis gave De = 1.4 x 10 9cm2/s and Ds = 2.0 x 10 6cm2/s for 4 = 4 x 10 3 cm and 4 = 3.6 x 10 2 cm [205]. These values for the diffusion coefficients are reasonable compared with those of aqueous gels and lipid membranes. 

In the transport across a phospholipid bilayer by passive diffusion, the permeability of the neutral form of a molecule is 10X times greater than that of the charged form. For the epithelium, the discrimination factor is 105. The basement membrane (Fig. 2.5) allows passage of uncharged molecules more readily than charged species by a factor of 10 [76]. 

Bhat, M. Toledo-Velasquez, D. Wang, L. Y. Malanga, C. J. Ma, J. K. H. Rojanasakul, Y., Regulation of tight junction permeability by calcium mediators and cell cytoskeleton in rabbit tracheal epithelium, Pharm. Res. 10, 991-997 (1993). 

Walter,E. Janich, S. Roessler, B.J. Hilfinger,J.M. Amidon, G. L., HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium In vitro-in vivo correlation with permeability data from rats and humans, J. Pharm. Sci. 85, 1070-1076 (1996). 

Morimoto et al. [33] demonstrated that the ocular absorption of hydrophilic compounds over a wide range of molecular weights could be increased by 2 and 10 mM sodium taurocholate and sodium taurodeoxycholate in a dose-dependent manner. The compounds were glutathione (307 Da), 6-carboxyfluorescein (376 Da), FTTC-dextran (4 kDa), and insulin (5.7 kDa). Of the two bile salts, sodium taurodeoxycholate was more effective. At 10 mM, this bile salt increased the permeability of 6-carboxyfluorescein from 0.02% to 11%, glutathione from 0.08% to 6%, FITC-dextran from 0% to 0.07%, and insulin from 0.06% to 3.8%. Sodium taurocholate, on the other hand, increased the permeability to 0.13%, 0.38%, 0.0011%, and 0.14%, respectively. Taurodeoxycholate was more effective than taurocholate in the nasal epithelium as well [202], This difference in activities can possibly be attributed to their micelle-forming capability, which is higher for taurodeoxycholate, a dihydroxy bile salt [190],... 

UB Kompella, KJ Kim, VHL Lee. (1992). Paracellular permeability of a chloride secreting epithelium. Proc Int Symp Controlled Release 19 425-426. 

JA Zadunaisky, B Spinowitz. (1977). Drugs affecting the transport and permeability of the corneal epithelium. In S Dikstein, ed. Drugs and Ocular Tissues. Basel Krager, pp 57-78. 

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