Application of cell co-culture models in absorption of oral drug

LI Ying; ZHU Chunyan

doi:10.3969/j.issn.1006-0111.2015.04.001

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2015 > 33(4): 289-292,327

LI Ying, ZHU Chunyan. Application of cell co-culture models in absorption of oral drug[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 289-292,327. doi: 10.3969/j.issn.1006-0111.2015.04.001

Citation:

LI Ying, ZHU Chunyan. Application of cell co-culture models in absorption of oral drug[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 289-292,327. doi: 10.3969/j.issn.1006-0111.2015.04.001

Application of cell co-culture models in absorption of oral drug

doi: 10.3969/j.issn.1006-0111.2015.04.001

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

Received Date: 2014-09-21
Rev Recd Date: 2015-03-05

Abstract

Cell co-culture system can better simulate the inner environment of human body, predict drug transport and metabolism in intestinal environment and increase the relation between in vitro cell model and integral animal test. In recent years, co-culture cell model plays an increasingly important role in evaluating the absorption of oral drugs, which becomes the highlight in the evaluation of drug oral absorption during new drug discovery. This essay summarized co-culture cell model which simulates intestinal environment and their application, and looked into the future of their application in evaluating oral drug intestinal absorption during oral drug discovery.
- cell model,
- co-culture system,
- oral drug,
- intestinal absorption,
- new drug screening

References

[1]	Fröhlich E, Roblegg E. Models for oral uptake of nanoparticles in consumer products[J]. Toxicology, 2012,291(1-3):10-17.
[2]	Chen XM, Elisia I, Kitts DD. Defining conditions for the co-culture of Caco-2 and HT29-MTX cells using Taguchi design[J]. J Pharmacol Toxicol Meth, 2010, 61(3):334-342.
[3]	Behrens I, Stenberg P, Artursson P, et al. Transport of lipophilic drug molecules in a new mucus-secreting cell culture model based on HT29-MTX cells[J]. Pharm Res, 2001,18 (8):1138-1145.
[4]	Walter E, Janich S, Roessler BJ, et al. HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans[J]. J Pharm Sci,1996,85(10):1070-1076.
[5]	Woitiski CB, Sarmento B, Carvalho RA, et al. Facilitated nanoscale delivery of insulin across intestinal membrane models[J]. Int J Pharm, 2011, 412(1-2):123-131.
[6]	Rocha RA, Vélez D, Devesa V. In vitro evaluation of intestinal fluoride absorption using different cell models[J]. Toxicol Lett,2012,210(3):311-317.
[7]	Mahler GJ, Shuler ML, Glahn RP. Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell culture model used to predict iron bioavailability[J]. J Nutr Biochem, 2009, 20(7):494-502.
[8]	Vázquez M, Calatayud M, Vélez D, et al. Intestinal transport of methylmercury and inorganic mercury in various models of Caco-2 and HT29-MTX cells[J].Toxicology,2013,311(3):147-153.
[9]	Sam M, Linda F, David JB, et al. Melittin as a Permeability EnhancerⅡ: In vitro investigations in human mucus secreting intestinal monolayers and rat colonic mucosae [ J]. Pharm Res, 2007, 24(7): 1346-1356.
[10]	Maresca M, Mahfoud R, Garmy N, et al. The Mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells[J]. Amer Soc Nutr Sci,2002,132 (9):2723-2731.
[11]	Gagnon M, Zihler Berner A, Chervet N, et al. Comparison of the Caco-2, HT-29 and the mucus-secreting HT29-MTX intestinal cell models to investigate Salmonella adhesion and invasion[J].J Microbiol Meth,2013,94(3):274-279.
[12]	Lai YH, D'Souza MJ. Microparticle transport in the human intestinal M cell model[J]. J Drug Target, 2008, 16(1): 36-42.
[13]	Corr SC, Gahan CC, Hill C. M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis[J]. FEMS Immunol MedMicrobiol, 2008, 52(1): 2-12.
[14]	des Rieux A, Ragnarsson EG, Gullberg E, et al. Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium[J]. Eur J Pharm Sci, 2005,25(4-5): 455-465.
[15]	Gullberg E, Leonard M, Karlsson J, et al. Expression of specific markers and particle transport in a new human intestinal M-cell model[J]. Biochem Biophys Res Commun, 2000, 279(3): 808-813.
[16]	des Rieux A, Fievez V, Théate I, et al. An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells[J]. Eur J Pharm Sci, 2007, 30(5): 380-391.
[17]	Garinot M, Fiévez V, Pourcelle V, et al. PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination[J]. J Control Release, 2007, 120(3):195-204.
[18]	Pielage JF, Cichon C, Greune L, et al. Reversible differentiation of Caco-2 cells reveals galectin-9 as a surface marker molecule for human follicle-associated epithelia and M cell-like cells[J]. Int J Biochem Cell Biol, 2007, 39(10): 1886-1901.
[19]	Kadiyala I, Looa Y, Roy K, et al. Transport of chitosan-DNA nanoparticles in human intestinal M-cell model versus normal intestinal enterocytes[J]. Eur J Pharm Sci, 2010, 39(1-3):103-109.
[20]	Tonry JH, Popov SG, Narayanan A, et al. In vivo murine and in vitro M-like cell models of gastrointestinal anthrax[J]. Microb Infect, 2013, 15(1):37-44.
[21]	Antunes F, Andrade F, Araújo F, et al. Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs[J]. Eur J Pharm Biopharm, 2013, 83(3): 427-435.
[22]	Araújo F, Sarmento B.Towards the characterization of an in vitro triple co-culture intestine cell model for permeability studies[J].Int J Pharm, 2013, 458(1):128-134.
[23]	Han HK, Oh DM, Amidon GL. Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPepT1 cells overexpressing a human peptide transporter[J]. Pharm Res,1998,15(9):1382-1386.
[24]	Annette B, Sibylle H, Kayoshi S, et al. Cell cultures as tools in biopharmacy[J]. Eur J Pharm Sci, 2000, 11 (Suppl2):S51-S60.
[25]	Tang F, Horie K, Borchardt RT. Are MDCK cells transfected with MRP2 gene a good model of the human intestinal mucosa?[J].Pharm Res, 2002, 19(6):773-779.
[26]	Cummins CL, Jacobsen W, Christians U, et al.CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam[J]. J Pharmacol Exper Therap, 2004,308 (1):143-155.
[27]	Korjamo T, Monkkonen J, Uusitalo J, et al. Metabolic and efflux properties of Caco-2 cells stably transfected with nuclear receptors[J].Pharm Res, 2006, 23(9):1991-2001.
[28]	Agarwal S, Jain R, Pal D,et al. Functional characterization of peptide transporters in MDCKII-MDR1 cell line as a model for oral absorption studies[J]. Int J Pharm, 2007, 332(1-2):147-152.
[29]	Xiaokui H, Qi L, Changyuan W, et al. Enhancement effect of P-gp inhibitors on the intestinal absorption and antiproliferative activity of bestatin[J]. Eur J Pharm Sci, 2013, 50(3-4):420-428.
[30]	Hellinger E, Bakk ML, Pócza P,et al. Drug penetration model of vinblastine-treated Caco-2 cultures[J]. Eur J Pharmaceut Sci, 2010, 41(1): 96-106.
[31]	Brayden DJ, Griffin J. Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers[J].Vet Res Commun, 2008, 32(1):93-106.
[32]	Darwich AS, Neuhoff S, Jamei M, et al. Interplay of metabolism and transport in determining oral drug absorption and gut wall metabolism: a simulation assessment using the "advanced dissolution, absorption, metabolism (ADAM)" model[J]. Curr Drug Metabol,2010,11(9):716-729.
[33]	Schmohl M, Schneiderhan-Marra N, Baur N, et al. Characterization of immunologically active drugs in a novel organotypic co-culture model of the human gut and whole blood[J]. Int Immunopharmacol, 2012, 14(4):722-728.
[34]	Clayburgh DR, Shen L, Turner JR. A porous defense: the leaky epithelial barrier in intestinal disease[J]. Lab Invest, 2004, 84(3),282-291.
[35]	Yasuda M, Furuyashiki T, Nakamura T,et al. Immunomodulatory activity of enzymatically synthesized glycogen and its digested metabolite in a co-culture system consisting of differentiated Caco-2 cells and RAW264.7 macrophages[J].Food Funct, 2013,4(9), 1387-1393.
[36]	Leonard F, Collnot EM, Lehr CM. A three-dimensional coculture of enterocytes, monocytes and dendritic cells to model inflamed intestinal mucosa in vitro[J]. Mol Pharm, 2013, 7(6), 2103-2119.
[37]	陈晓清,焦红,程树军,等.Caco-2细胞与肠道菌共培养初建体外肠道共生模型[J].中山大学学报(医学科学版),2012,33(1):121-126.
[38]	Le Hégarat L, Huet S, Fessard V. A co-culture system of human intestinal Caco-2 cells and lymphoblastoid TK6 cells for investigating the genotoxicity of oral compounds[J]. Mutagenesis,2012,27(6):631-636.

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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

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Application of cell co-culture models in absorption of oral drug

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

Received Date: 2014-09-21

Rev Recd Date: 2015-03-05

Key words:

Abstract: Cell co-culture system can better simulate the inner environment of human body, predict drug transport and metabolism in intestinal environment and increase the relation between in vitro cell model and integral animal test. In recent years, co-culture cell model plays an increasingly important role in evaluating the absorption of oral drugs, which becomes the highlight in the evaluation of drug oral absorption during new drug discovery. This essay summarized co-culture cell model which simulates intestinal environment and their application, and looked into the future of their application in evaluating oral drug intestinal absorption during oral drug discovery.

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Reference (38)

[1]	Fröhlich E, Roblegg E. Models for oral uptake of nanoparticles in consumer products[J]. Toxicology, 2012,291(1-3):10-17.
[2]	Chen XM, Elisia I, Kitts DD. Defining conditions for the co-culture of Caco-2 and HT29-MTX cells using Taguchi design[J]. J Pharmacol Toxicol Meth, 2010, 61(3):334-342.
[3]	Behrens I, Stenberg P, Artursson P, et al. Transport of lipophilic drug molecules in a new mucus-secreting cell culture model based on HT29-MTX cells[J]. Pharm Res, 2001,18 (8):1138-1145.
[4]	Walter E, Janich S, Roessler BJ, et al. HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans[J]. J Pharm Sci,1996,85(10):1070-1076.
[5]	Woitiski CB, Sarmento B, Carvalho RA, et al. Facilitated nanoscale delivery of insulin across intestinal membrane models[J]. Int J Pharm, 2011, 412(1-2):123-131.
[6]	Rocha RA, Vélez D, Devesa V. In vitro evaluation of intestinal fluoride absorption using different cell models[J]. Toxicol Lett,2012,210(3):311-317.
[7]	Mahler GJ, Shuler ML, Glahn RP. Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell culture model used to predict iron bioavailability[J]. J Nutr Biochem, 2009, 20(7):494-502.
[8]	Vázquez M, Calatayud M, Vélez D, et al. Intestinal transport of methylmercury and inorganic mercury in various models of Caco-2 and HT29-MTX cells[J].Toxicology,2013,311(3):147-153.
[9]	Sam M, Linda F, David JB, et al. Melittin as a Permeability EnhancerⅡ: In vitro investigations in human mucus secreting intestinal monolayers and rat colonic mucosae [ J]. Pharm Res, 2007, 24(7): 1346-1356.
[10]	Maresca M, Mahfoud R, Garmy N, et al. The Mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells[J]. Amer Soc Nutr Sci,2002,132 (9):2723-2731.
[11]	Gagnon M, Zihler Berner A, Chervet N, et al. Comparison of the Caco-2, HT-29 and the mucus-secreting HT29-MTX intestinal cell models to investigate Salmonella adhesion and invasion[J].J Microbiol Meth,2013,94(3):274-279.
[12]	Lai YH, D'Souza MJ. Microparticle transport in the human intestinal M cell model[J]. J Drug Target, 2008, 16(1): 36-42.
[13]	Corr SC, Gahan CC, Hill C. M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis[J]. FEMS Immunol MedMicrobiol, 2008, 52(1): 2-12.
[14]	des Rieux A, Ragnarsson EG, Gullberg E, et al. Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium[J]. Eur J Pharm Sci, 2005,25(4-5): 455-465.
[15]	Gullberg E, Leonard M, Karlsson J, et al. Expression of specific markers and particle transport in a new human intestinal M-cell model[J]. Biochem Biophys Res Commun, 2000, 279(3): 808-813.
[16]	des Rieux A, Fievez V, Théate I, et al. An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells[J]. Eur J Pharm Sci, 2007, 30(5): 380-391.
[17]	Garinot M, Fiévez V, Pourcelle V, et al. PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination[J]. J Control Release, 2007, 120(3):195-204.
[18]	Pielage JF, Cichon C, Greune L, et al. Reversible differentiation of Caco-2 cells reveals galectin-9 as a surface marker molecule for human follicle-associated epithelia and M cell-like cells[J]. Int J Biochem Cell Biol, 2007, 39(10): 1886-1901.
[19]	Kadiyala I, Looa Y, Roy K, et al. Transport of chitosan-DNA nanoparticles in human intestinal M-cell model versus normal intestinal enterocytes[J]. Eur J Pharm Sci, 2010, 39(1-3):103-109.
[20]	Tonry JH, Popov SG, Narayanan A, et al. In vivo murine and in vitro M-like cell models of gastrointestinal anthrax[J]. Microb Infect, 2013, 15(1):37-44.
[21]	Antunes F, Andrade F, Araújo F, et al. Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs[J]. Eur J Pharm Biopharm, 2013, 83(3): 427-435.
[22]	Araújo F, Sarmento B.Towards the characterization of an in vitro triple co-culture intestine cell model for permeability studies[J].Int J Pharm, 2013, 458(1):128-134.
[23]	Han HK, Oh DM, Amidon GL. Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPepT1 cells overexpressing a human peptide transporter[J]. Pharm Res,1998,15(9):1382-1386.
[24]	Annette B, Sibylle H, Kayoshi S, et al. Cell cultures as tools in biopharmacy[J]. Eur J Pharm Sci, 2000, 11 (Suppl2):S51-S60.
[25]	Tang F, Horie K, Borchardt RT. Are MDCK cells transfected with MRP2 gene a good model of the human intestinal mucosa?[J].Pharm Res, 2002, 19(6):773-779.
[26]	Cummins CL, Jacobsen W, Christians U, et al.CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam[J]. J Pharmacol Exper Therap, 2004,308 (1):143-155.
[27]	Korjamo T, Monkkonen J, Uusitalo J, et al. Metabolic and efflux properties of Caco-2 cells stably transfected with nuclear receptors[J].Pharm Res, 2006, 23(9):1991-2001.
[28]	Agarwal S, Jain R, Pal D,et al. Functional characterization of peptide transporters in MDCKII-MDR1 cell line as a model for oral absorption studies[J]. Int J Pharm, 2007, 332(1-2):147-152.
[29]	Xiaokui H, Qi L, Changyuan W, et al. Enhancement effect of P-gp inhibitors on the intestinal absorption and antiproliferative activity of bestatin[J]. Eur J Pharm Sci, 2013, 50(3-4):420-428.
[30]	Hellinger E, Bakk ML, Pócza P,et al. Drug penetration model of vinblastine-treated Caco-2 cultures[J]. Eur J Pharmaceut Sci, 2010, 41(1): 96-106.
[31]	Brayden DJ, Griffin J. Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers[J].Vet Res Commun, 2008, 32(1):93-106.
[32]	Darwich AS, Neuhoff S, Jamei M, et al. Interplay of metabolism and transport in determining oral drug absorption and gut wall metabolism: a simulation assessment using the "advanced dissolution, absorption, metabolism (ADAM)" model[J]. Curr Drug Metabol,2010,11(9):716-729.
[33]	Schmohl M, Schneiderhan-Marra N, Baur N, et al. Characterization of immunologically active drugs in a novel organotypic co-culture model of the human gut and whole blood[J]. Int Immunopharmacol, 2012, 14(4):722-728.
[34]	Clayburgh DR, Shen L, Turner JR. A porous defense: the leaky epithelial barrier in intestinal disease[J]. Lab Invest, 2004, 84(3),282-291.
[35]	Yasuda M, Furuyashiki T, Nakamura T,et al. Immunomodulatory activity of enzymatically synthesized glycogen and its digested metabolite in a co-culture system consisting of differentiated Caco-2 cells and RAW264.7 macrophages[J].Food Funct, 2013,4(9), 1387-1393.
[36]	Leonard F, Collnot EM, Lehr CM. A three-dimensional coculture of enterocytes, monocytes and dendritic cells to model inflamed intestinal mucosa in vitro[J]. Mol Pharm, 2013, 7(6), 2103-2119.
[37]	陈晓清,焦红,程树军,等.Caco-2细胞与肠道菌共培养初建体外肠道共生模型[J].中山大学学报(医学科学版),2012,33(1):121-126.
[38]	Le Hégarat L, Huet S, Fessard V. A co-culture system of human intestinal Caco-2 cells and lymphoblastoid TK6 cells for investigating the genotoxicity of oral compounds[J]. Mutagenesis,2012,27(6):631-636.

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Application of cell co-culture models in absorption of oral drug

doi: 10.3969/j.issn.1006-0111.2015.04.001

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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