• Archives of Pharmacal Research
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• v.25 no.1
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• pp.86-92
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• 2002

The enhancement of paracellular transport of heparin disaccharide using several absorption enhancers across Caco-2 cell monolayers was tested . The cytotoxicity of these enhancers was also examined. The enhancing effects by Quillaja saponin, diponin glycyrrhizinate, $18{\beta}-glycyrrhetinic$ acid, sodium caprate and taurine were determined by changes in transepithelial electrical resistance (TEER) and the amount of heparin disaccharide transported across Caco-2 cell monolayers. Among the absorption enhancers, $18{\beta}-glycyrrhetinic$ acid arid taurine decreased TEER and increased the permeability of heparin disaccharide in a dose-dependent and time-dependent manner with little or negligible cytotoxicity. Our results indicate that these absorption enhancers can widen the tight junction, which is a dominant paracellular absorption route of hydrophilic compounds . It is highly possible that these absorption enhancers can be applied as pharmaceutical excipients to improve the transport of macromolecules and hydrophilic drugs having difficulty in permeability across the intestinal epithelium.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.419.2-420
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• 2002

Caco-2 is a cell line derived from the human colon adenocarcinoma and often used as a model for studying intestinal drug absorption. It has been well-known that a strong correlation holds between in vitro permeability across Caco-2 cell monolayers and in vivo bioavailability for various drugs. but the correlation curves varied depending on laboratories. The permeabilities of drugs across Caco-2 cell monolayers have been measured under different agitation conditions. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.415.1-415.1
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• 2002

Apical to basal transport of organic cations (OCs) such as tributylmethylammonium (TBuMA), triethyimethylammonium (TEMA). 1-methyl-4-phenylpyridinium (MPP), and berberine across Caco-2 cell monolayers was measured to elucidate the intestinal absorption of OCs. Basal to apical transport of MPP and berberine was larger than apical to basal transport and showed temperature dependency and concentration dependency. indicating that MPP and berberine are secreted into the inteslinal lumen. (omitted)

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.51-62
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• 2022

Lactobacillus rhamnosus SKG34 (LrSKG34), a potential probiotic strain, was successfully isolated from Sumbawa Mare's milk. Our previous studies showed that the strain is resistant to gastrointestinal conditions, possesses antioxidant activity, and lowers blood cholesterol levels. Further clarification of the potential probiotic characteristics and safety assessment are necessary. This study aimed to evaluate the adhesion of LrSKG34 to Caco-2 cell monolayers and its effect on mucosal integrity in vitro. We also examined the LrSKG34 safety profile based on antimicrobial susceptibility testing, haemolytic activity determination, Caco-2 cell monolayer translocation evaluation, and in vivo investigation of the effect of LrSKG34 on the physiology, biochemical markers, and histopathological appearance of major organs in an animal model. LrSKG34 attached to Caco-2 cell monolayers and maintained mucosal integrity in vitro. The typical resistance of lactobacilli to ciprofloxacin, gentamicin, vancomycin, trimethoprim-sulfamethoxazole, and metronidazole was confirmed for LrSKG34. No haemolytic activity was observed on blood agar plates, and no LrSKG34 translocation was observed in Caco-2 cell monolayers. Administration of LrSKG34 to Sprague-Dawley rats did not adversely affect body weight. No abnormalities in hematological parameters, serum biochemistry levels, or histopathological structures of major organs were observed in LrSKG34-treated rats. Collectively, the results implicate LrSKG34 as a promising and potentially safe probiotic candidate for further development.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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• pp.111-116
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• 2005

The unstirred water layer (UWL), which has been known to exist in the boundary of the intestinal lumen and intestinal wall, often behaves as an absorption barrier especially for lipophilic drugs. The intestinal absorption of drugs is often characterized using Caco-2 cell monolayers grown on Transwell polycarbonate membranes. The permeability $(P_{app})$ of drugs across the cell monolayer might be influenced by the agitation of the donor compartment, since the width of UWL on the surface of the cell monolayer would be reduced by the agitation. In this study, the effect of agitation of the donor compartment with 60 rpm on the permeability was measured for 12 drugs with a wide range of lipophilicity and permeability. The $P_{app}$ of mannitol, tributylmethyl ammonium, cimetidine, ranitidine, hydrocortisone, benzylpenicillin and loxoprofen was not influenced by the agitation, while the $P_{app}$ of theophylline, propranolol, YH439, phenylpropanolamine and testosterone was increased by the agitation. There was a significant correlation between the increase of $P_{app}$ by agitation and the lipophilicity for the compounds having $P_{app}>2{\times}10^{-5}$ cm/sec. No correlation was observed for the difference in $P_{app}$ by agitation and the molecular weight, or lipophilicity of the drugs. Therefore, the agitation rate of the donor compartment in the Caco-2 cell monolayer study should be carefully controlled in order to estimate $P_{app}$ reproducibly especially for lipophilic drugs.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.318-322
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• 2006

Many quaternary ammonium salts are incompletely absorbed after their oral administration and may also be actively secreted into the intestine. However, the underlying mechanism(s) that control the transport of these cations across the intestinal epithelium is not well understood. In this study, the mechanism of absorption of quaternary ammonium salts was investigated using Caco-2 cell monolayers, a human colon carcinoma cell line. Tributylmethylammonium (TBuMA) was used as a model quaternary ammonium salts. When TBuMA was administrated at a dose of 13.3 imole/kg via iv and oral routes, the AUC values were $783.7{\pm}43.6\;and\;249.1{\pm}28.0{\mu}mole\;min/L$ for iv and oral administration, indicating a lower oral bioavailability of TBuMA $(35.6\%)$. The apparent permeability across Caco-2 monolayers from the basal to the apical side was 1.3 times (p<0.05) greater than that from the apical to the basal side, indicating a net secretion of TBuMA in the intestine. This secretion appeared to be responsible for the low oral bioavailability of the compound, probably mediated by p-gp (p-glycoprotein) located in the apical membrane. In addition, the uptake of TBuMA by the apical membrane showed a $Na^+$ dependency. Thus, TBuMA appears to absorbed via a $Na^+$ dependent carrier and is then secreted via p-gp related carriers.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.234.3-235
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• 2003

The aim of this study is to evaluate the permeability of PEG-conjugated salmon calcitonin (sCT) across monolayers of Caco-2 cells that represent a model of the intestinal barrier. Caco-2 cells were grown to confluency on a permeable polycarbonate membrane to permit transport through it. Permeability experiments were performed with native-sCT and PEG-conjugated sCT (PEG M.W. 2000) at various concentrations (5uM, 10uM, 25uM, 50uM, 100uM) in the apical to basolateral direction. The barrier properties were assessed by detecting transport of markder molecules ($^3$H-mannitol) and by measuring transepithelial electrical resistance (TEER). (omitted)

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.108.2-109
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• 2001

• Food Science and Biotechnology
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• v.17 no.3
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• pp.675-678
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• 2008

Permeability of resveratrol, piceid, rhapontigenin, and rhaponticin in Caco-2 cell assays using high-performance liquid chromatography were compared. Caco-2 cell monolayers were used to evaluate the transport rates of stilbene analogues from the apical to the basolateral sides. All stilbenes experimented in this study were transported to the basolateral side by times. For comparing the permeability of 4 stilbenes, we calculated the slope of the cumulative concentration of each stilbene in basolateral sides over time, resulting in those values of resveratrol, piceid, rhapontigenin, and rhaponticin with $3.766{\times}10^{-5}$, $4.330{\times}10^{-6}$, $5.430{\times}10^{-5}$, and $2.458{\times}10^{-5}\;{\mu}M/sec$, respectively. Apparent permeability coefficient of resveratrol and rhapontigenin were calculated to $9.994{\times}10^{-6}$ and $1.441{\times}10^{-6}\;cm/sec$, respectively, while those of piceid and rhaponticin were to $1.149{\times}10^{-7}$ and $6.523{\times}10^{-7}\;cm/sec$, respectively. These results suggest that aglycones would be absorbed more effectively than glycosides in stilbenoids.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.225.2-225.2
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• 2001