Biorelevant media resistant co-culture model mimicking permeability of human intestine

Antoine, D; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

doi:10.1016/j.ijpharm.2015.01.028

Cited by 31 publications

(12 citation statements)

References 24 publications

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“…These models are usually used to evaluate the permeability of the API alone since they are not sufficiently robust to support either biorelevant media or “real” formulations. Indeed, to better approach the physiological conditions, mucus-producing HT29-MTX cells and M cells inducing Raji B cells were introduced into the Caco-2 monolayer [8,9,10,11,12,13]. Although in vivo studies cannot necessarily provide insight into regional differences in drug absorption, this has been attempted to be addressed in rats by the single-pass intestinal perfusion technique or, with appropriate adjustments, the closed-loop Doluisio method [14].…”

Section: Introductionmentioning

confidence: 99%

Drug Transport across Porcine Intestine Using an Ussing Chamber System: Regional Differences and the Effect of P-Glycoprotein and CYP3A4 Activity on Drug Absorption

et al. 2019

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Drug absorption across viable porcine intestines was investigated using an Ussing chamber system. The apparent permeability coefficients, Papp,pig, were compared to the permeability coefficients determined in humans in vivo, Peff,human. Eleven drugs from the different Biopharmaceutical Classification System (BCS) categories absorbed by passive diffusion with published Peff,human values were used to test the system. The initial experiments measured Papp,pig for each drug after application in a Krebs–Bicarbonate Ringer (KBR) buffer and in biorelevant media FaSSIF V2 and FeSSIF V2, mimicking fasted and fed states. Strong sigmoidal correlations were observed between Peff,human and Papp,pig. Differences in the segmental Papp,pig of antipyrine, cimetidine and metoprolol confirmed the discrimination between drug uptake in the duodenum, jejunum and ileum (and colon); the results were in good agreement with human data in vivo. The presence of the P-gp inhibitor verapamil significantly increased Papp,pig across the ileum of the P-gp substrates cimetidine and ranitidine (p < 0.05). Clotrimazole, a potent CYP3A4 inhibitor, significantly increased Papp,pig of the CYP3A4 substrates midazolam, verapamil and tamoxifen and significantly decreased the formation of their main metabolites. In conclusion, the results showed that this is a robust technique to predict passive drug permeability under fasted and fed states, to identify regional differences in drug permeability and to demonstrate the activity of P-gp and CYP3A4.

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Section: Introductionmentioning

confidence: 99%

Drug Transport across Porcine Intestine Using an Ussing Chamber System: Regional Differences and the Effect of P-Glycoprotein and CYP3A4 Activity on Drug Absorption

et al. 2019

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“…Monolayers of HT29-MTX cells have previously been used as a permeability model for studying the effect of mucus on the permeation of drugs (Hagesaether et al, 2013;Pontier et al, 2001). A coculture of Caco-2 and HT29-MTX cells has been suggested as more realistic in-vitro models of the human intestine, due to mucus secretion and adjustable paracellular and P-gp mediated transport (Antoine et al, 2015;Woitski et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

An in vitro study of mucoadhesion and biocompatibility of polymer coated liposomes on HT29-MTX mucus-producing cells

Adamczak

Hagesæther

Smistad

et al. 2016

International Journal of Pharmaceutics

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Drug delivery to the oral cavity poses a significant challenge due to the short residence time of the formulations at the site of action. From this point of view, nanoparticulate drug delivery systems with ability to adhere to the oral mucosa are advantageous as they could increase the effectiveness of the therapy. Positively, negatively and neutrally charged liposomes were coated with four different types of polymers: alginate, low-ester pectin, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose. The mucoadhesion was studied using a novel in vitro method allowing the liposomes to interact with a mucus-producing confluent HT29-MTX cell-line without applying any external force. MTT viability and paracellular permeability tests were conducted on the same cell-line. The alginate-coated liposomes achieved a high specific (genuine) mucin interaction, with a low potential of cell-irritation. The positively charged uncoated liposomes achieved the highest initial mucoadhesion, but also displayed a higher probability of cell-irritation. The chitosan-coated liposomes displayed the highest potential for long lasting mucoadhesion, but with the drawback of a higher general adhesion (tack) and a higher potential for irritating the cells.

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“…Lucifer Yellow results were consistent with these findings, as the rate of lucifer yellow transport greatly increased in correspondence with dropping TEER values. These results are not surprising and are in line with reported literature, in which all of these components at the tested concentrations (with the exception of FA) had little effect on monolayer viability up to 1 hour [170]. While FA is known to be toxic to cells, Antoine et al…”

Section: Viability Studiessupporting

confidence: 91%

Mechanistic studies and modeling of the impact of lipids and emulsifiers on oral drug absorption in vivo

Speciner¹

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be where I am today. I would like to thank my parents, Roberta and Norm Speciner, for all their love and support and for raising me with the belief that there were no limits to what I could accomplish in life. I would also like to thank my significant other, Stephan Bassil, for supporting me through the best and worst times of my graduate work, including braving Mass Ave traffic, on occasion, to drive me to school to troubleshoot the HPLC or take a time point. During my time at Northeastern I received support from several professors. I would like to sincerely thank my advisor, Dr. Rebecca Carrier, for having faith in me and giving me the opportunity to work on this project and for reminding me that no matter what, everything was going to be okay. And it was! I would also like to thank my other committee members, Dr. Mansoor Amiji and Dr. Debra Auguste for their feedback and insightful questions. Another important aspect of school is the team of graduate students that you work side by side with on a daily basis. I would like to thank my lab mate, and partner in crime, Oljora Rezhdo for all the collaboration, scientific discussions, and late nights in the lab. You are a great friend and I'm glad I got to share this graduate journey with you. I would also like to thank the other graduate students in 104 Mugar, Jackie Lock and Taylor Carlson, for your help, friendship, and making the lab a fun place to be. I had many great undergraduate and masters students who helped with in vivo studies, without which they would not have been successful. Thank you to

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Biorelevant media resistant co-culture model mimicking permeability of human intestine

Cited by 31 publications

References 24 publications

Drug Transport across Porcine Intestine Using an Ussing Chamber System: Regional Differences and the Effect of P-Glycoprotein and CYP3A4 Activity on Drug Absorption

Drug Transport across Porcine Intestine Using an Ussing Chamber System: Regional Differences and the Effect of P-Glycoprotein and CYP3A4 Activity on Drug Absorption

An in vitro study of mucoadhesion and biocompatibility of polymer coated liposomes on HT29-MTX mucus-producing cells

Mechanistic studies and modeling of the impact of lipids and emulsifiers on oral drug absorption in vivo

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