Estimating Intestinal Mucosal Permeation of Compounds Using Caco‐2 Cell Monolayers

Gao, Jinnian; Hugger, Erin; Beck-Westermeyer, Melissa S.; Borchardt, Ronald T.

doi:10.1002/0471141755.ph0702s08

Cited by 37 publications

(46 citation statements)

References 25 publications

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“…The Papp values of propranolol and atenolol tested in the Caco-2 cell monolayers were 2.54 x 10 -5 cm/s and 3.35 x 10 -7 cm/s, respectively, as determined by HPLC (Figure 3) and were comparable to the results reported in literature (Chong et al, 1997;Yee, 1997;Walle et al, 1999;Gao et al, 2001). Our results indicated that the Caco-2 model could be used to evaluate the transport of cinnamon extract.…”

Section: Stability Of the Reaction Systemsupporting

confidence: 89%

Cinnamon effectively inhibits the activity of leukemia stem cells

Guan¹,

Mc²,

Rb³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Cinnamon is the main component of Sanyangxuedai, which is one of the effective traditional Chinese medicines for treating malignancies. Leukemia is a prevalent malignant disease that Sanyangxuedai has been used to treat. Although successful in several studies, there is a lack of solid evidence as to why Sanyangxuedai has an effect on leukemia, and little is known about the underlying mechanisms. In this study, the active ingredients of cinnamon were isolated, purified, and identified. The transwell transport pool formed with the Caco-2 cell model was used to filter the active ingredients of cinnamon by simulating the gastrointestinal barrier in vitro. Moreover, the cell morphology, cell cycle status, apoptosis status, and antigenic variation of the cell surface antigens were observed and measured in K562 cells after treatment with the active ingredients of cinnamon. Our results showed that 50-75 µM was a safe concentration of cinnamon extract for treatment of K562 cells for 72 h. The cinnamon extract caused growth inhibition of K562 cells. Cinnamon extract seemed to arrest the cells at the G1 stage and increased the apoptosis rate significantly. Interestingly, cinnamon extract treatment upregulated the expression of erythroid and myeloid differentiation antigens and downregulated that of the megakaryocytic differentiation antigens in a dose-dependent manner. Our findings indicate that cinnamon extract from Sanyangxuedai may be effective for treating leukemia.

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Section: Stability Of the Reaction Systemsupporting

confidence: 89%

Cinnamon effectively inhibits the activity of leukemia stem cells

Guan¹,

Mc²,

Rb³

et al. 2016

Genet. Mol. Res.

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“…Bidirectional transport of [ 14 C]erythromycin across MDCK-MDR1 was carried out as described previously (Gao et al, 2000), with some modifications. The purpose of the transport experiment was to determine that erythromycin was a good substrate for P-gp with a good efflux potential which could be used to test the functionality of P-gp in rabbit corneas.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Erythromycin in Rabbit Corneas after Single-Dose Infusion: Role of P-Glycoprotein as a Barrier to in Vivo Ocular Drug Absorption

Dey

Gunda²,

Mitra³

2004

J Pharmacol Exp Ther

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Efflux pump like P-glycoprotein (P-gp) is known to be a major barrier to drug delivery. Functional P-glycoprotein has been recently identified in cornea and corneal cell lines. Thus, it is probable that P-glycoprotein may restrict in vivo ocular drug absorption, resulting in low ocular bioavailability. Experiments were designed using New Zealand albino (New Zealand White) rabbits to assess inhibitors of P-gp efflux to increase drug absorption. Anesthetized rabbits were given constant topical infusions of [14 C]erythromycin in the presence and absence of inhibitors. Testosterone, verapamil, quinidine, and cyclosporine A were selected as P-gp inhibitors. Transport experiments were conducted in Madin-Darby canine kidney cells transfected with the human mdr1 gene (MDCK-MDR1). Erythromycin exhibited significant efflux out of MDCK-MDR1 cells, suggesting that erythromycin is a good substrate for P-gp. Ocular pharmacokinetic studies were conducted using a topical single-dose infusion method. Maximum inhibition of P-gp mediated efflux was observed with 500 M testosterone. Area under the curve (AUC) 0-ϱ of erythromycin with 500 M testosterone was almost 4 times higher than AUC 0-ϱ without any inhibitor. Rate of elimination (k 10 ) for erythromycin and those with inhibitors was found to be similar (141 Ϯ 23 min), suggesting that elimination pathways were not altered. All the inhibitors were found to be nontoxic. Verapamil also inhibited the efflux pump with moderate change in AUC 0-ϱ and C max compared with control. Thus, P-gp is found to be active in vivo, and it restricts topical erythromycin absorption across the cornea, which can be inhibited by known P-gp inhibitors. Therefore, ocular bioavailability of P-gp substrates can be significantly enhanced by proper selection of P-gp inhibitors.

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“…Bidirectional transport experiments were performed as previously described 20 with some modifications. All experiments were done at 378C with constant mixing in a shaking water bath (60 rpm).…”

Section: Transport Experimentsmentioning

confidence: 99%

“…1 filter inserts (six-well) and maintained in high-glucose Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum, 0.1 mM nonessential amino acids, 2 mM L-glutamine solution, 100 U/mL penicillin, and 100 mg/mL streptomycin as described previously. 20 Experiments were conducted on these cells after 6 days of culture. The functional expression of P-gp transporter in the transfected cells was checked using Western blotting techniques and […”

Section: Introductionmentioning

confidence: 99%