In vitro 3D human small intestinal villous model for drug permeability determination

2012 ◽  
Vol 109 (9) ◽  
pp. 2173-2178 ◽  
Author(s):  
Jiajie Yu ◽  
Songming Peng ◽  
Dan Luo ◽  
John C. March
2021 ◽  
Vol 140 ◽  
pp. 110054
Author(s):  
Pablo Gallego-Lobillo ◽  
Alvaro Ferreira-Lazarte ◽  
Oswaldo Hernández-Hernández ◽  
Mar Villamiel

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.


2014 ◽  
Vol 55 (2) ◽  
pp. 381-390 ◽  
Author(s):  
Motohiro Yamauchi ◽  
Kensuke Otsuka ◽  
Hisayoshi Kondo ◽  
Nobuyuki Hamada ◽  
Masanori Tomita ◽  
...  

2018 ◽  
Vol 154 (6) ◽  
pp. S-858-S-859
Author(s):  
Jenni Firrman ◽  
Elliot S. Friedman ◽  
William C. Strange ◽  
Jung-Jin Lee ◽  
Kyle Bittinger ◽  
...  

2021 ◽  
Vol 95 ◽  
Author(s):  
E.S. El-Wakil ◽  
H.F. Abdelmaksoud ◽  
T.S. AbouShousha ◽  
M.M.I. Ghallab

Abstract Our work aimed to evaluate the possible effect of Annona muricata (Graviola) leaf extract on Trichinella spiralis in in vitro and in vivo studies. Trichinella spiralis worms were isolated from infected mice and transferred to three culture media – group I (with no drugs), group II (contained Graviola) and group III (contained albendazole) – then they were examined using the electron microscope. In the in vivo study, mice were divided into five groups: GI (infected untreated), GII (prophylactically treated with Graviola for seven days before infection), GIII (infected and treated with Graviola), GIV (infected and treated with albendazole) and GV (infected and treated with a combination of Graviola plus albendazole in half doses). Drug effects were assessed by adults and larvae load beside the histopathological small intestinal and muscular changes. A significant reduction of adult and larval counts occurred in treated groups in comparison to the control group. Histopathologically, marked improvement in the small intestinal and muscular changes was observed in treated groups. Also, massive destruction of the cultured adults’ cuticle was detected in both drugs. This study revealed that Graviola leaves have potential activity against trichinellosis, especially in combination with albendazole, and could serve as an adjuvant to anti-trichinellosis drug therapy.


2018 ◽  
Vol 98 (3) ◽  
pp. 463-476 ◽  
Author(s):  
Namalika D. Karunaratne ◽  
Dawn A. Abbott ◽  
Ravindra N. Chibbar ◽  
Pierre J. Hucl ◽  
Curtis J. Pozniak ◽  
...  

The objective of the study was to measure the effect of wheat market class and cultivar on starch digestibility using an in vitro model that mimics the chicken digestive tract and relate it to grain characteristics. The study evaluated 18 wheat cultivars from eight western Canadian wheat classes and, each cultivar was replicated four times. Samples were subjected to gastric and small intestine (SI) digestion phases and each sample was assayed in triplicate; glucose release was measured in SI phase. Starch granule distribution, amylose, total starch, crude protein (CP), ash, and non-starch polysaccharides (NSP) were analyzed in all wheat samples. Small intestinal phase times of 15, 60, and 120 min were chosen to approximate digestion in the terminal duodenum, jejunum, and ileum. Starch digestibility of wheat classes ranged as follows: 15 min — 33.1% to 49.1%, 60 min — 80.2% to 93.3%, and 120 min — 92.4% to 97.6%. Starch digestibility positively correlated with CP, ash, NSP, and proportion of large granules, whereas it negatively correlated with total starch, and proportion of small and medium granules. In conclusion, market class and cultivar of western Canadian wheat affects both rate and extent of starch digestibility and it is related to various grain characteristics.


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