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  • Articles  (4)
  • permeability  (4)
  • Arabidopsis thaliana
  • Korea
  • Springer  (4)
  • American Geophysical Union (AGU)
  • Chemistry and Pharmacology  (4)
  • 1
    ISSN: 1573-904X
    Keywords: drug delivery systems ; skin alternatives ; transdermal drug delivery ; permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To test the barrier function of a bio-engineered human skin (BHS) using three model drugs (caffeine, hydrocortisone, and tamoxifen) in vitro. To investigate the lipid composition and microscopic structure of the BHS. Methods. The human skin substitute was composed of both epidermal and dermal layers, the latter having a bovine collagen matrix. The permeability of the BHS to three model drugs was compared to that obtained in other percutaneous testing models (human cadaver skin, hairless mouse skin, and EpiDerm™). Lipid analysis of the BHS was performed by high performance thin layered chromatrography. Histological evalulation of the BHS was performed using routine H&E staining. Results. The BHS mimicked human skin in terms of lipid composition, gross ultrastructure, and the formation of a stratum corneum. However, the permeability of the BHS to caffeine, hydrocortisone, and tamoxifen was 3-4 fold higher than that of human cadaver skin. Conclusions. In summary, the results indicate that the BHS may be an acceptable in vitro model for drug permeability testing.
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  • 2
    ISSN: 1573-904X
    Keywords: tracheal epithelial cells ; air-interfaced culture ; ion transport ; drug transport ; permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The objective of this study was to investigate how culture conditions would affect the morphological, functional, and permeability characteristics of rabbit tracheal epithelial cell layers being considered for drug transport studies. Methods. Rabbit tracheocytes were isolated by protease treatment and plated onto collagen-treated permeable supports at 1.3 × 106 cells/cm2. After 24 hr, cell layers were cultured either air-interfaced (AIC) on their apical surface or under conventional liquid covered conditions (LCC). Results. Scanning electron microscopy revealed mature cilia in AIC cell layers and ciliated cells denuded of cilia in LCC cell layers. Compared with LCC, AIC cell layers (n = 20) achieved a significantly higher peak equivalent short-circuit current (74.1 ± 6.5 vs. 51.6 ± 3.4 µA/cm2), a higher potential difference (70.9 ± 2.8 vs. 60.5 ± 3.0 mV), and a lower peak transepithelial electrical resistance (1.1 ± 0.03 vs. 1.5 ± 0.02 kohms,cm2). About 70% of the short-circuit current in AIC was amiloride-sensitive whereas 〈10% was furosemide-sensitive, similar to that found in native tissue. The corresponding values in LCC were 50% and 46%. The permeability of both AIC and LCC to lipophilic solutes (dexamethasone and propranolol) was similar, whereas the permeability of hydrophilic solutes (mannitol, sucrose, and albuterol) in AIC was only half that in LCC. Conclusions. Given the striking similarity in morphological and functional characteristics of the AIC to those in the in vivo situation, the AIC is favored as an in vitro model for future drug transport studies.
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  • 3
    ISSN: 1573-904X
    Keywords: Cereport ; bradykinin B2 receptor ; human ; brain endothelium ; permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study Cereport (RMP-7, bradykinin B2 agonist) effects on human brain microvascular endothelial cell (HBMEC) monolayer permeability. Methods. HBMEC grown on transwell membranes were exposed to Cereport. The monolayer permeability was determined with [I4C]-inulin (MW. 5,200) and [3H]-dextran (MW. 70,000). Results. Cereport increased the HBMEC permeability to [l4C]-inulin, but not to [3H]-dextran. The effect was transient, maximal at 15 min (i.e., 79.3% increase), and polarized to the basolateral membrane. An inverted U, dose-response curve was observed with active concentrations of Cereport from 0.01 to 0.5 nmol/L, the plateau maximal effect between 0.5 and 10 nmol/L, and loss of activity at the highest concentration, i.e., 20 nmol/L. Cyclic AMP-specific phosphodiesterase 3 (PDE3) inhibitor rolipram (10 μmol/L) abolished Cereport effects, while cGMP-specific PDE5 inhibitor, zaniprast (50 μmol/L) enhanced by 31 % (p 〈 0.05) the effect of 0.1 nmol/L Cereport. Unlabeled Cereport displaced [12 5I]-bradykinin and/or [125I]-Cereport from the basolateral side. There was no specific Cereport binding to the apical side. Conclusions. Cereport exerts specific time, dose and size dependent actions on HMBEC monolayer that are restricted to the basolateral membrane. Its effects can be further modulated through changes in cAMP and cGMP second messenger systems.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 9 (1992), S. 1113-1122 
    ISSN: 1573-904X
    Keywords: thyrotropin releasing hormone ; buccal mucosa ; metabolism ; permeability ; in vitro tissue integrity ; transport pathways ; rate-limiting barrier
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The transport of thyrotropin releasing hormone (TRH) in rabbit buccal mucosa in vitro has been investigated with respect to (a) rate and type of metabolism of TRH on mucosal and serosal sides of buccal mucosa, (b) mechanism of TRH transport including charge effect on its permeability, and (c) pathway and rate-limiting regions of TRH movement. In addition, the integrity of excised buccal mucosa has been evaluated for purposes of in vitro solute diffusion experiments using tissue ATP level data, transmission electron microscopy, and TRH transport kinetic data. The results indicate that excised rabbit buccal mucosa can be used for TRH diffusion studies for approximately 6 hr. In addition, TRH apparently traverses buccal mucosa by simple diffusion with a steady-state permeability of about 10−7 cm/sec, and this permeability is independent of pH. Moreover, the primary pathway appears to be via the intercellular space in the rate-limiting barrier, i.e., the upper 50 µm of the epithelium. Finally, TRH is degraded predominantly by deamidase activity, which is followed by, to a lesser degree, carboxypeptidase metabolism.
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