Open AccessRobotically handled whole-tissue culture system for the screening of oral drug formulations
Author(s) -
Thomas von Erlach,
Sarah Saxton,
Yulei Shi,
Daniel Minahan,
Daniel Reker,
Farhad Javid,
Young-Ah Lucy Lee,
Carl M. Schoellhammer,
Tina Esfandiary,
Cody Cleveland,
Lucas Booth,
Jiaqi Lin,
Hannah Levy,
Sophie M. Blackburn,
Alison Hayward,
Robert Langer,
Giovanni Traverso
Publication year - 2020
Publication title -
nature biomedical engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.961
H-Index - 56
ISSN - 2157-846X
DOI - 10.1038/s41551-020-0545-6
Subject(s) - bioavailability , drug , pharmacology , in vivo , absorption (acoustics) , pharmacokinetics , drug delivery , medicine , chemistry , biology , microbiology and biotechnology , materials science , organic chemistry , composite material
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.