Investigating the Impact of Crohn's Disease on the Bioaccessibility of a Lipid-Based Formulation with an in Vitro Dynamic Gastrointestinal Model

Angela Effinger, Mark Mcallister, Irena Tomaszewska, Caitriona M. O'Driscoll, Mark Taylor, Steve Gomersall, James Heaton, Kieran L. Smith, Inese Sarcevica, Sam L. Young, Nikoletta Fotaki

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The aim of the study was to investigate the impact of Crohn's disease (CD) on the performance of a lipid-based formulation of ciprofloxacin in a complex gastrointestinal simulator (TIM-1, TNO) and to compare the luminal environment in terms of bile salt and lipid composition in CD and healthy conditions. CD conditions were simulated in the TIM-1 system with a reduced concentration of porcine pancreatin and porcine bile. The bioaccessibility of ciprofloxacin was similar in simulated CD and healthy conditions considering its extent as well as its time course in the jejunum and ileum filtrate. Differences were observed in terms of the luminal concentration of triglycerides, monoglycerides, and fatty acids in the different TIM-1 compartments, indicating a reduction and delay in the lipolysis of formulation excipients in CD. The quantitative analysis of bile salts revealed higher concentrations for healthy conditions (standard TIM-1 fasted-state protocol) in the duodenum and jejunum TIM-1 compartments compared to published data in human intestinal fluids of healthy subjects. The reduced concentrations of bile salts in simulated CD conditions correspond to the levels observed in human intestinal fluids of healthy subjects in the fasted state.A lipidomics approach with ultra performance liquid chromatography (UPLC)/mass spectrometry (MS) has proven to be a time-efficient method to semiquantitatively analyze differences in fatty acid and bile salt levels between healthy and CD conditions. The dynamic luminal environment in CD and healthy conditions after administration of a lipid-based formulation can be simulated using the TIM-1 system. For ciprofloxacin, an altered luminal lipid composition had no impact on its performance indicating a low risk of altered performance in CD patients.

Original languageEnglish
Pages (from-to)1530-1543
Number of pages14
JournalMolecular Pharmaceutics
Issue number4
Early online date3 Mar 2021
Publication statusPublished - 5 Apr 2021

Bibliographical note

Funding Information:
The authors would like to thank Sudesha Wanigaratne and Aidan Harper for their assistance with TIM-1 studies and Neil Dawson for his assistance with light microscopy measurements. This work has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 674909 (PEARRL).

Publisher Copyright:
© 2021 American Chemical Society.

Copyright 2021 Elsevier B.V., All rights reserved.


  • bile salts
  • Crohn's disease
  • fatty acids
  • lipid-based formulation
  • lipidomics
  • luminal environment
  • TIM-1 TNO

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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