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Caco-2 Cell Line (caco-2 + cell_line)
Selected AbstractsFacile Synthesis and In-Vitro Antitumor Activity of Some Pyrazolo[3,4- b]pyridines and Pyrazolo[1,5- a]pyrimidines Linked to a Thiazolo[3,2- a]benzimidazole MoietyARCHIV DER PHARMAZIE, Issue 1 2010Hatem A. Abdel-Aziz Abstract The key precursor E -3-(N,N -dimethylamino)-1-(3-methylthiazolo[3,2- a]benzimidazol-2-yl)prop-2-en-1-one 4 was synthesized in good yield using Gold's reagent. The reaction of enaminone 4 with 5-amino-3-aryl-1 - phenylpyrazoles 5a, b in refluxing acetic acid in the presence of sulphuric acid, yielded pyrazolo[3,4- b]pyridines 7a, b. Similarly, pyrazolo[1,5- a]pyrimidines 10a, b and 14a,f were prepared by reaction of enaminone 4 with 5-amino-1H -pyrazoles 8a, b and 12a,f, respectively. The structure of pyrazolo[1,5- a]pyrimidine 10b was determined by X-ray diffraction. The synthesized compounds were tested for their in-vitro antitumor activity against the colon cancer cell line CaCo-2; their cytotoxicity against the normal fibroblast cell line BHK was explored as well. Some of the tested compounds exhibited cell growth inhibitory activity. The significant antitumor activity of compound 14f against the CaCo-2 cell line (IC50 = 0.5 ,g/mL) was coupled with a lower toxicity against BHK (IC50 = 2.3 ,g/mL). [source] Transport of levovirin prodrugs in the human intestinal Caco-2 cell lineJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2006Fujun Li Abstract The transport of 10 amino acid ester prodrugs of levovirin (LVV) was investigated in the human intestinal Caco-2 cell line in order to overcome the poor oral bioavailability of LVV, an investigational drug for the treatment of hepatitis C infection. The prodrugs were designed to improve the permeability of LVV across the intestinal epithelium by targeting the di/tri-peptide carrier, PepT1. Caco-2 cell monolayers were employed to study the transport and hydrolysis properties of the prodrugs. Among all mono amino acid ester prodrugs studied, the LVV-5,-(L)-valine prodrug (R1518) exhibited the maximum increase (48-fold) in permeability with nearly complete conversion to LVV within 1 h. Di-amino acid esters did not offer significant enhancement in permeability comparing with mono amino acid esters and exhibited slower conversion to LVV in Caco2 cell monolayers. Pharmacokinetic screening studies of the prodrugs in rats yielded the highest fold increase (6.9-fold) of AUC with R1518 and in general displayed a similar trend to that observed in increases of permeability in Caco-2 cells. Mechanisms involved in the Caco-2 cell transport of R1518 were also investigated. Results of bi-directional transport studies support the involvement of carrier-mediated transport mechanisms for R1518, but not for the LVV-5,-(D)-valine prodrug or LVV. Moreover, the permeability of R1518 was found to be proton dependent. PepT1-mediated transport of R1518 was supported by results of competitive transport studies of R1518 with the PepT1 substrates enalapril, Gly-Sar, valganciclovir, and cephalexin. R1518 was also found to inhibit the permeability of valganciclovir and cephalexin. These results suggest that R1518 is a PepT1 substrate as well as an inhibitor. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:1318,1325, 2006 [source] Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines, and rat jejunumJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004Giuseppina Sandri The influence of the molecular weight on mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid (1878, 693 and 202 kDa) has been evaluated. The mucoadhesive properties were investigated using buccal and vaginal porcine mucosa by means of a tensile stress method and using rat jejunum by means of an inclined plane method. The mucoadhesive performances observed using animal tissues were compared with the mucoadhesive properties observed using submaxillary or gastric mucin dispersions. The penetration enhancement properties were investigated using porcine buccal epithelium membrane or vaginal tissue and a cell monolayer (Caco-2 cell line). Chitosan hydrochloride, already described as a penetration enhancer towards buccal and vaginal mucosae and Caco-2 cell monolayers, was used as reference. Aciclovir (acyclovir), a poorly soluble and absorbable drug, commonly used in the treatment of Herpes simplex virus (type I and II), was used as the model drug. Unlike chitosan hydrochloride, which does not show any mucoadhesive potential at pH close to neutrality (buccal and intestinal), all hyaluronic acid grades show mucoadhesive properties in all the environments considered (buccal, vaginal and intestinal). In all cases, a decrease in molecular weight of hyaluronic acid produced an increase in the mucoadhesive performance. The hyaluronic acid with the lowest molecular weight (202 kD) exhibited the best penetration enhancement properties, that, depending on the substrate under consideration, was either comparable with or even better than chitosan hydrochloride. Therefore, this grade would be the most promising for buccal, vaginal and intestinal delivery of aciclovir. [source] Transport characteristics of candesartan in human intestinal Caco-2 cell lineBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2009Lingjie Zhou Abstract The intestinal absorptive characteristics and the efflux mechanisms of candesartan (CDS), a novel angiotensin II type 1 receptor blocker, were investigated. The Caco-2 cells were used as models of the intestinal mucosa to assess uptake and transport of CDS. The determination of CDS was performed by HPLC-Flu. In the Caco-2 cells, the uptake and absorptive transport of CDS were pH-independent (in the pH range 6.0,8.0). Passive membrane diffusion dominates the absorptive transport behavior of CDS across Caco-2 cells, while secretory transport was a concentration-dependent and saturable process. In the presence of cyclosporin A and verapamil, potent inhibitors of P-glycoprotein (P-gp), the Pratio decreased from 3.8 to 2.3 and 1.8, respectively, and permeation of apical to basolateral was enhanced. Overall, the current study suggests that efflux transporters are capable of mediating the absorption and secretion of CDS, and they may play significant roles in limiting the oral absorption of CDS. Copyright © 2009 John Wiley & Sons, Ltd. [source] Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines, and rat jejunumJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004Giuseppina Sandri The influence of the molecular weight on mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid (1878, 693 and 202 kDa) has been evaluated. The mucoadhesive properties were investigated using buccal and vaginal porcine mucosa by means of a tensile stress method and using rat jejunum by means of an inclined plane method. The mucoadhesive performances observed using animal tissues were compared with the mucoadhesive properties observed using submaxillary or gastric mucin dispersions. The penetration enhancement properties were investigated using porcine buccal epithelium membrane or vaginal tissue and a cell monolayer (Caco-2 cell line). Chitosan hydrochloride, already described as a penetration enhancer towards buccal and vaginal mucosae and Caco-2 cell monolayers, was used as reference. Aciclovir (acyclovir), a poorly soluble and absorbable drug, commonly used in the treatment of Herpes simplex virus (type I and II), was used as the model drug. Unlike chitosan hydrochloride, which does not show any mucoadhesive potential at pH close to neutrality (buccal and intestinal), all hyaluronic acid grades show mucoadhesive properties in all the environments considered (buccal, vaginal and intestinal). In all cases, a decrease in molecular weight of hyaluronic acid produced an increase in the mucoadhesive performance. The hyaluronic acid with the lowest molecular weight (202 kD) exhibited the best penetration enhancement properties, that, depending on the substrate under consideration, was either comparable with or even better than chitosan hydrochloride. Therefore, this grade would be the most promising for buccal, vaginal and intestinal delivery of aciclovir. [source] Expression levels of human P-glycoprotein in In Vitro cell lines: correlation between mRNA and protein levels for P-glycoprotein expressed in cellsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2009Yoshiyuki Shirasaka Abstract The purpose of this study was to investigate the correlation between mRNA and protein levels for P-glycoprotein (P-gp) expressed in various cell lines to validate the estimation of P-gp activity from its mRNA levels. P-gp expression levels in various cell monolayers, normal, P-gp-induced, P-gp-highly induced, (multidrug resistance, MDR) MDR1-knockdown (A2-2) and MDR1-knockdown (B2-2) Caco-2 cells and MDCKII/MDR1 cells, were quantified by real-time quantitative polymerase chain reaction (PCR) and western blot analysis. Both mRNA and protein levels of P-gp were lowest in the MDR1-knockdown (B2-2) Caco-2 cells, followed by the MDR1-knockdown (A2-2) Caco-2, normal Caco-2, P-gp-induced Caco-2 and P-gp-highly induced Caco-2 cells, and highest in the MDCKII/MDR1 cells. Except for the MDCKII/MDR1 cells, the protein levels of P-gp in all Caco-2 cell lines showed a linear correlation with its mRNA levels; however, although the MDR1 mRNA level in MDCKII/MDR1 cells was much higher than in the P-gp-highly induced Caco-2 cells, the protein levels were almost the same in both cells. From these findings, it was suggested that P-gp activity in MDCKII/MDR1 cells could not be estimated from its mRNA levels. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||