Robotically handled whole-tissue culture system for the screening of oral drug formulations
| Autor: | Alison Hayward, Farhad Javid, Daniel Minahan, Sophie Blackburn, Young-Ah Lucy Lee, Hannah Levy, Daniel Reker, Thomas von Erlach, Cody Cleveland, Sarah Saxton, Yunhua Shi, Robert Langer, Giovanni Traverso, Carl M. Schoellhammer, Jiaqi Lin, Tina Esfandiary, Lucas Booth |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Gastrointestinal tract business.industry media_common.quotation_subject Biomedical Engineering Medicine (miscellaneous) Bioengineering Pharmacology Intestinal absorption Computer Science Applications Bioavailability 03 medical and health sciences Tissue culture 030104 developmental biology 0302 clinical medicine In vivo Cell culture Drug delivery Medicine business 030217 neurology & neurosurgery Biotechnology media_common |
| Zdroj: | Nature Biomedical Engineering. 4:544-559 |
| ISSN: | 2157-846X |
| Popis: | 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. A robotically handled culture system using porcine gastrointestinal tissue explants for the high-throughput interrogation of the gastrointestinal tract predicts the absorption of oral drugs in the human gut better than Caco-2 Transwells. |
| Databáze: | OpenAIRE |
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