Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs

Antunes, Filipa; Andrade, Fernanda; Araújo, Francisca; Ferreira, Domingos; Sarmento, Bruno

doi:10.1016/j.ejpb.2012.10.003

Cited by 235 publications

(191 citation statements)

References 39 publications

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“…Several modifications have been made to more closely mimic the heterogeneity of the intestinal epithelium; e.g., co-culturing Caco-2 and HT29 cells introduces the presence of mucin-secreting goblet cells and provides a physiological transport barrier [42,43,44]. Co-culturing Caco-2, HT29, and Raji B cells may more closely resemble intestinal mucosa [48]. Thus, more research is needed for the development of a reliable and replicable methodology to generate data may better predict in vivo nutrient/drug absorption.…”

Section: Discussionmentioning

confidence: 99%

Cell Culture Model for Examining Fat-Soluble Nutrient Absorption <i>In Vitro</i>

Kamil¹,

Blumberg²,

Chen³

2017

JFNR

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Permeable support systems (PS) are employed in in vitro nutrient absorption studies but data are absent on their efficacy compared to conventional cell culture models (CONV). The in vivo absorption of fat soluble nutrients is influenced by its delivery vehicle, yet a fundamental understanding of the influence of the vehicle on cells in culture is lacking. We compared the efficacy of lutein absorption in Caco-2 cells cultured with CONV and PS, and examined the role of micelles, the physiological vehicle within the small intestine. After plating for 2 and 21 d to attain confluence and differentiation in CONV and PS, respectively, cells were treated with lutein in micelles or ethanol. After incubation, lutein in cell lysate, as well as apical and basolateral mediums, were quantified by HPLC-UV. After 24 h, cellular lutein in CONV was ≥460 and 8% greater in ethanol and micelle, respectively, than in PS. However, the intracellular AUC over time was only different for ethanol (P ≤ 0.05). In PS, 0.15% of micellized lutein was secreted into the basolateral medium in contrast to 0.016% of lutein in ethanol. The absorption of lutein (uptake + secretion), independent of the vehicle, in CONV increased in a linear manner with dose (0.35 to 4 or to 14.6 µg/mL for ethanol or micelle, respectively), while that in PS peaked at 1.18 μg/mL. Caco-2 cells cultured in PS grow to display the phenotype and function of small intestine enterocytes and suggest this in vitro platform generates information closest to the natural physiology of the absorptive process. However, although the CONV has the physiology of colonic tissue, it appears to display a greater efficacy for lutein uptake by Caco-2 cells and so can provide a more rapid, preliminary method for nutrient absorption studies.

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Section: Discussionmentioning

confidence: 99%

Cell Culture Model for Examining Fat-Soluble Nutrient Absorption <i>In Vitro</i>

Kamil¹,

Blumberg²,

Chen³

2017

JFNR

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“…187 To combat this, co-culture systems, model inflammation and tissue culture are being developed by scientists to give in vivo quality answers with in vitro tests. [188][189][190] "The end of surprise would be the end of science. To this extent, the scientist must constantly see and hope for surprises" -Robert Friedel (Excerpt from Adapt by Tim Hartford)…”

Section: Subcutaneous Implantationmentioning

confidence: 99%

Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

Wickham¹

2015

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Linköping 2015Cover: Scanning Electron Microscopy image of a mesenchymal cell on polycaprolactone fibers.During the course of the research presented in this thesis, Abeni Wickham, was enrolled in Forum Scientium, a multidisciplinary graduate school at Linköping University. ColophonThis thesis is not only the summation of 5 years of research, but also a material manifestation of my happiness.It has not been straightforward and I have had numerous failures, disappointments and doubts. These have always been positive moments, as each difficult moment gave me the chance to choose a different path to still achieve my research goals.I have spent the past few years fighting for what I love the most; answering the questions that I ask myself every day. I have been lucky to have two supervisors, Daniel and Bo who pushed me to be better scientifically and family/friends who kept me grounded.During this work, I found who I really am; this thesis is a representation of me.ii Abstract Nature has had millions of years to perfect the structural components of the human body, but has also produced the dysfunctions that result in the cancers and diseases, which ruin that perfection. Congenital heart defects, and myocardial infarction lead to scarring that remodels heart muscle, decreasing the contractility of the heart, with profound consequences for the host. Regenerative medicine is the study of strategies to return diseased body parts to their evolutionarily optimum structure.Cells alone cannot develop into functional tissue, as they require mechanical support and chemical signals from the extracellular matrix in order to play the correct role in the body. In order to imitate the process of tissue formation optimized by nature, scaffolds are developed as the architectural support for tissue regeneration. To mimic the elasticity and strength seen in the heart muscle is one of the major scientific conundrums of our time. The development of new multifunctional materials for scaffolds is an accepted solution for repairing failing heart muscle. In this thesis I accept the notion that endogenous cardiac cells can play a major role in addressing this problem, if we can attract them to the site of defect or injury and make them proliferate. I then proceed to show how improving on a commonly used synthetic polymer was used to develop two new biomaterials.Polycaprolactone (PCL) fibers and sheets were studied for their ability to adsorb proteins based on their surface energies. We found that although the wettability of the PCL might be similar to positive controls for cell attachment, the large differences in surface energies may account for the increased serum protein adsorption and limit cell adhesion. The effect of fiber morphology was then investigated with respect to proliferation of mesenchymal stem cells and cardiac progenitor cells. PCL was also mechanically enhanced with thiophene conjugated single walled carbon nanotubes (T-CNT); where small concentrations of the T-CNT allowed for a 2.5 fold increase in the percentage of elong...

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“…Several adapted in vitro models based on colorectal adenocarcinoma Caco-2 cells have been developed in the last decade to test drug permeability across the intestinal barrier [8,9,16,19]. Among all these models, Caco-2 monoculture and co-culture of Caco-2 cells with Burkitt lymphoma B cells (Raji cells)…”

Section: Transport Experimentsmentioning

confidence: 99%

“…Previous authors have developed numerous strategies to obtain M-cell like in vitro models [8][9][10][11][12]. This work includes the development of an in vitro model of M cells based on the strategy of co-cultivating Caco-2 cells with Raji cells (B lymphocytes derived from Burkitt cell lymhoma) [9].…”

Section: Introductionmentioning

confidence: 99%

Graphical Abstracts

Publisher¹

2014

CTMC

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Nanotechnology is providing a new therapeutic paradigm by enhancing drug efficacy and preventing side-effects. Edelfosine is a synthetic ether lipid analogue of platelet activating factor with high antitumor activity. The encapsulation of this potent antitumor drug in lipid nanoparticles increases its oral bioavailability; moreover, it prevents the hemolytic and gastrointestinal side-effects of the free drug. The literature points towards lymphatic absorption of lipid nanoparticles after oral administration, and previous in vitro and in vivo studies stress the protection against toxicity that these nanosystems provide.The present study is intended to assess the permeability of lipid nanoparticles across the intestinal barrier.Caco-2 monoculture and Caco-2/Raji co-culture were used as in vitro models of enterocytes and Microfold cells respectively. Results showed that free drug is internalized and possibly metabolized in enterocytes. These results do not correlate with those observed in vivo when edelfosine-lipid nanoparticles were administered orally in mice, which suggests that the microfold model is not a good model to study the absorption of edelfosine-lipid nanoparticles across the intestinal barrier in vitro.

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Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs

Cited by 235 publications

References 39 publications

Cell Culture Model for Examining Fat-Soluble Nutrient Absorption <i>In Vitro</i>

Cell Culture Model for Examining Fat-Soluble Nutrient Absorption <i>In Vitro</i>

Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

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