Robotically Handled Whole-tissue Culture System for the Screening of Oral Drug Formulations

Overview

Journal Nat Biomed Eng

Publisher Springer Nature

Specialty Biomedical Engineering

Date 2020 Apr 29

PMID 32341538

Citations 11

Authors

Thomas von Erlach

Sarah Saxton

Yunhua Shi

Daniel Minahan

Daniel Reker

Farhad Javid

Young-Ah Lucy Lee

Carl Schoellhammer

Tina Esfandiary

Cody Cleveland

Lucas Booth

Jiaqi Lin

Hannah Levy

Sophie Blackburn

Alison Hayward

Robert Langer

Giovanni Traverso

Affiliations

Soon will be listed here.

Abstract

Monolayers of cancer-derived cell lines are widely used in the modelling of the gastrointestinal (GI) absorption of drugs and in oral drug development. However, they do not generally predict drug absorption in vivo. Here, we report a robotically handled system that uses large porcine GI tissue explants that are functionally maintained for an extended period in culture for the high-throughput interrogation (several thousand samples per day) of whole segments of the GI tract. The automated culture system provided higher predictability of drug absorption in the human GI tract than a Caco-2 Transwell system (Spearman's correlation coefficients of 0.906 and 0.302, respectively). By using the culture system to analyse the intestinal absorption of 2,930 formulations of the peptide drug oxytocin, we discovered an absorption enhancer that resulted in a 11.3-fold increase in the oral bioavailability of oxytocin in pigs in the absence of cellular disruption of the intestinal tissue. The robotically handled whole-tissue culture system should help advance the development of oral drug formulations and might also be useful for drug screening applications.

Citing Articles

Evaluation of Drug Permeation Enhancement by Using In Vitro and Ex Vivo Models.

Steyn J, Haasbroek-Pheiffer A, Pheiffer W, Weyers M, van Niekerk S, Hamman J Pharmaceuticals (Basel). 2025; 18(2).

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Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC - What is Coming Next?.

Bohley M, Leroux J Adv Sci (Weinh). 2024; 11(33):e2400843.

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Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.

Shi Y, Reker D, Byrne J, Kirtane A, Hess K, Wang Z Nat Biomed Eng. 2024; 8(3):278-290.

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A Modular Microfluidic Organoid Platform Using LEGO-Like Bricks.

Carvalho D, Kip A, Tegel A, Stich M, Krause C, Romitti M Adv Healthc Mater. 2024; 13(13):e2303444.

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A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety.

Srinivasan S, Alshareef A, Hwang A, Byrne C, Kuosmanen J, Ishida K Sci Adv. 2023; 9(51):eadj3003.

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