This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 956851.

Prof. Patrick Augustijns

Prof. Patrick Augustijns holds a Pharmacy degree, a Master in Medical Sciences and a Ph.D. in Pharmaceutical Sciences. Prior to becoming a professor at the University of Leuven (Belgium), he performed postdoctoral research at the University of Kansas and at GSK (North Carolina). In 2003, Patrick Augustijns became chairman of Drug Delivery and Disposition.

The laboratory has a strong track record in the biorelevant profiling of intestinal drug absorption, covering all underlying processes including dissolution, precipitation, degradation and permeation. For this purpose, a wide range of simulation models are available, including the in vitro Caco-2 cell culture system, the Ussing chambers system and the in situ intestinal perfusion system. In addition, Drug Delivery and Disposition is able and licensed to perform whole animal absorption and pharmacokinetic experiments. Physiology-based pharmacokinetic modelling is available to extrapolate experimental data to human pharmacokinetics. One of the lab’s major research topics involves the aspiration and in-depth characterization of gastrointestinal fluids, including the evaluation of intraluminal drug and formulation behavior in humans. The latter involves the bio-relevant and predictive evaluation of absorption-enabling strategies, including solubilisation and supersaturation of poorly soluble drugs. All aspiration and absorption studies are supported by well-developed analytical equipment (LC-UV, -fluo, -MS/MS) to assess the concentrations of endogenous compounds found in the intestinal fluids, as well as of drugs and excipients in biological matrices. Patrick Augustijns is (co)author of ± 350 peer-reviewed papers in international journals and more than 300 presentations at scientific meetings. Patrick Augustijns presently supervises 3 postdocs, 5 PhD students, and 2 PhD students as copromotor. Since 2008, he is AAPS-fellow (an honorary distinction by the American Association of Pharmaceutical Scientists). In January 2019, he was awarded an honorary doctorate from Uppsala University.


In vivo and in vitro assessment of colonic drug disposition

NSAIDs such as celecoxib and sulindac play a critical role in the treatment of colorectal cancer, yet it is not understood how sufficiently high concentrations are reached in colonic tissue. After developing a protocol to reliably collect colonic biopsies and contents, we demonstrated that an incomplete small intestinal absorption of celecoxib and sulindac enables gut driven drug accumulation in caecal tissue. Due to a lack of insight into the colonic disposition, colon-targeted compounds and formulations often suffer from inconsistent performance. Moreover, in vitro systems that address the complexity of the colonic environment are limited, and often focus on permeability and stability assessment, but do not consider the importance of accumulation. This is specifically crucial for colon-targeted drugs since they often aim to directly target the epithelium or immune cells of the lamina propria and are less desired to enter the blood stream.

To this end, we used relevant non-clinical absorption models such as the Caco-2 cell line, the EpiIntestinalTM, and the Ussing chambers setup with excised intestinal tissue to clarify the accumulation behaviour. We showed that the favourable physicochemical properties (lipophilicity, pKa,..) of celecoxib likely underlie its extensive accumulation in mucus and tissue compared to sulindac, which can potentially result in sustained and prolonged tissue exposure. We also observed that drug uptake assays under relevant colon conditions, i.e. suspension, can more closely mimic the in vivo accumulation behaviour. As such, the integration of these accumulation assays in the screening of novel drugs can improve the predictive value in the evaluation of local effects, and can especially be beneficial towards determining the needed drug dose to reach therapeutic concentration in humans.