ABSTRACT
Permeability is a key factor in the bioavailability of oral drugs. Therefore, in the early stage of drug discovery, accurate and efficient evaluation of drug permeability is essential. The parallel artificial membrane permeability assay (PAMPA) with Caco-2 cells model was used by the industry as early evaluation methods. At present, the Ussing chamber rat model is also widely used. This review summarizes the human data for the in vivo single-pass perfusion technique (Loc-I-Gut) – the gold standard, and then focuses on the basic principles, experimental operation, and efficiency of the three in vitro methods, with correlation to the effective permeability coefficient (Peff) and fractional absorbed (Fa) in man. We provide recommendations for the use of proper permeability methods at different stages in drug discovery and development.
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OBJECTIVE: To study the absorption characteristics of allicin in rat intestinal tract.METHODS: An HPLC method was established to determine the content of allicin in rat entericus, and Ussing chamber system was used to investigate the absorption characteristics of garlic spicy element of different concentrations in the duodenum, jejunum, ileum and colon of rats. RESULTS: An HPLC method was established to determine the content of allicin in rat intestinal liquid.The absorption rate constants of allicin in various intestinal segments of rats in the experimental concentration range increased with the increase of allicin concentration.Allicin showed linear absorption in different intestinal segments of rats, with regression correlation coefficients of greater than 0.96, indicating zero order absorption. CONCLUSION: Allicin has different absorption characteristics in different intestinal segments of rats and can be absorbed as prototype.
ABSTRACT
Intestinal permeability is one of key factors determing absorption of oral drug products. It is a big challenge to assess permeability of compounds with high accuracy and high efficacy during research and development process. In this review, the principles, strengths, weaknesses and advances of common intestinal permeability models are summarized, with focus on Ussing chamber and parallel artificial membrane permeability assay. In addition, future trends of permeability models are briefly discussed. This review may provide a reference to accessing permeability of lead compounds.
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Objective To investigate the effect of procyanidin on permeability of rodamin 123(R123)and fluorescein sodium (FS)via different intestinal mucosa in rat. Methods The cumulative permeability and the apparent permeability cofficient(Papp)of R123 and FS via rat intestinal membranes at the procyanidin concentration of 20 mg/L was evaluated by the method of Ussing Cham?ber. The concentrations of R123 and FS in the receptor samples were determined by fluorospectrophotometry. Results The absorptive directed permeability of R123 across all membranes was increased by co-administration of procyanidins,whereas that of the secretive direct was decreased. Compared with control group,the secretive directed permeability of R123 was significantly decreased in colon (P<0.01). Conclusion Procyanidin could inhibit the secretion of R123 on different intestinal mucosa which might be related to the inhibition of P-gp function.
ABSTRACT
Objective To investigate the effect of procyanidin on permeability of rodamin 123(R123)and fluorescein sodium (FS)via different intestinal mucosa in rat. Methods The cumulative permeability and the apparent permeability cofficient(Papp)of R123 and FS via rat intestinal membranes at the procyanidin concentration of 20 mg/L was evaluated by the method of Ussing Chamber. The concentrations of R123 and FS in the receptor samples were determined by fluorospectrophotometry. Results The absorptive directed permeability of R123 across all membranes was increased by co-administration of procyanidins, whereas that of the secretive direct was decreased. Compared with control group, the secretive directed permeability of R123 was significantly decreased in colon (P<0.01). Conclusion Procyanidin could inhibit the secretion of R123 on different intestinal mucosa which might be related to the inhibition of P-gp function.
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This study was conducted to evaluate an adapter-modified Ussing chamber for assessment of transport physiology in endoscopically obtained duodenal biopsies from healthy cats and dogs, as well as dogs with chronic enteropathies. 17 duodenal biopsies from five cats and 51 duodenal biopsies from 13 dogs were obtained. Samples were transferred into an adapter-modified Ussing chamber and sequentially exposed to various absorbagogues and secretagogues. Overall, 78.6% of duodenal samples obtained from cats responded to at least one compound. In duodenal biopsies obtained from dogs, the rate of overall response ranged from 87.5% (healthy individuals; n = 8), to 63.6% (animals exhibiting clinical signs of gastrointestinal disease and histopathological unremarkable duodenum; n = 15), and 32.1% (animals exhibiting clinical signs of gastrointestinal diseases and moderate to severe histopathological lesions; n = 28). Detailed information regarding the magnitude and duration of the response are provided. The adapter-modified Ussing chamber enables investigation of the absorptive and secretory capacity of endoscopically obtained duodenal biopsies from cats and dogs and has the potential to become a valuable research tool. The response of samples was correlated with histopathological findings.
Subject(s)
Animals , Biopsy/veterinary , Cat Diseases/physiopathology , Cats/physiology , Dog Diseases/physiopathology , Dogs/physiology , Duodenal Diseases/physiopathology , Duodenoscopy/veterinary , Duodenum/physiologyABSTRACT
BACKGROUND AND OBJECTIVES: Rhinovirus infection on the airway epithelial cells results in derangement in mucociliary clearance. However, the contribution of altered ion transport across the epithelial cells in rhinovirus-induced alteration in mucociliary clearance has not been studied yet. Thus, we aimed to investigate the effect of rhinovirus infection on the electrical property of airway epithelial cells. MATERIALS AND METHODS: Tracheal mucosae were harvested and digested with protease. The epithelial cells thus obtained were cultured in air-liquid interface method. Rhinvovirus-16s were infected for 1 hour on the epithelial cells and cultured for 48 hours thereafter. Transepithelial resistance was measured by a chopstick voltmeter and short circuit current was measured by Ussing chamber technique. The electrical properties of control and infection groups were compared. RESULTS: The change in the transepithelial resistance in the control group was 240 ohm.cm2, while it was 263 ohm.cm2 in the RV infected epithelium. The baseline short circuit current was 6.3 microEq.cm-2.h-1 in the control group and 7.2 microEq.cm-2.h-1 in the RV infected group. The difference was not significant. Change in short circuit current induced by mucosally applied amiloride and foskolin were not different significantly in both groups. CONCLUSION: The results of this study indicated that rhinovirus infection in the airway epithelial cells does not affect the electrical property, which reflects the function of ion channels in the epithelial cells.
Subject(s)
Amiloride , Epithelial Cells , Epithelium , Ion Channels , Ion Transport , Mucociliary Clearance , Mucous Membrane , RhinovirusABSTRACT
No abstract available.
Subject(s)
Adenosine Triphosphate/pharmacology , Animals , Anions/metabolism , Biological Transport/physiology , Biological Transport/drug effects , Calcium/metabolism , Cell Line , Cell Polarity/physiology , Cells, Cultured , Enzyme Inhibitors/pharmacology , Epithelial Cells/metabolism , Epithelial Cells/metabolism , Epithelial Cells/cytology , Fluorescent Dyes , Fura-2 , Horses , Receptors, Purinergic P2/metabolism , Thapsigargin/pharmacologyABSTRACT
This review introduces the basal elements and structures of Ussing chamber and it′s applications in the field of intestinal barrier function research.
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The rabbit cornea was studied in vitro in modified Ussing chambers to determine the effects of ion transport inhibitors and hydrogen peroxide(H2O2) on ion transport through the cornea by measuring the bioelectric properties. Apical(tear side, T side) addition of furosemide, bumetanide and SITS were ineffective on resting Isc(short circuit current). Apical addition of 1.0mM amiloride(Na+/H+ antiport inhibitor) and NPAA(Cl- channel blocker) markedly reduced the resting Isc, but basolateral(stromal side, S side) addition of amiloride was ineffective. The site of action of these agents was the apical membrane. H2O2, an oxygen free radical, markedly increased the lsc when was added to the T side, but S side addition of the H2O2 was ineffective. To determine the degree of cellular catalase participation in protection against H2O2 induced injury the cornea was pretreated with ATAZ for 30 min prior to H2O2 action. The increase of lsc by H2O2 was markedly potentiated after pretreatment with ATAZ on T side compared to that of S side addition. This result indicates that the corneal endothelial H2O2 may be largely degraded by catalase. When H2O2 was added to the T side, Isc was raised by increased ion transport. All ion transport inhibitors that were used inhibited the H2O2 effect on Isc. Moreover, amiloride and NPAA markedly inhibited induced lsc by H2O2. These results suggest that H2O2 stimulates the corneal epithelial ion transport and that its site of action is apical membrane Na+/H+ antiport system and CI- channel system.