Yael del Carmen Suárez-López, Alexandra Teleki

Affiliates

Department of Pharmacy, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

Abstract

Oral delivery of pharmaceuticals is the preferred route of administration due to its convenience and high patient compliance. Superparamagnetic iron oxide nanoparticles (SPION) hold great potential as orally delivered drugs for theragnostic of gastrointestinal conditions [1]. However, one critical issue of the oral delivery of nanoparticles, is the influence of the physicochemical properties of the gastrointestinal fluids on nanoparticle dynamics.

The gastrointestinal tract (GIT) is a complex system that consists of different organs, each with a different range of physicochemical characteristics like pH and biomolecule content. Furthermore, the environment of the GIT changes during illnesses such as inflammatory bowel disease [2].

In this project, an in vitro model was developed to simulate the passage of nanoparticles through the GIT. The in vitro model, IntesTiny, consists of three micromixers simulating the stomach, small intestine, and colon, respectively. Additionally, simulated fluids were developed to mimic a broad range of healthy and inflammatory environments of the GIT. Finally, the impact of the physicochemical composition of these fluids on nanoparticle size, surface charge, and biomolecule adsorption was investigated.

It was found that nanoparticle aggregation and surface charge increased with more acidic pH. Moreover, 30-50% of the lecithin adsorbed onto the SPION surface. As a result, media with high lecithin concentration (≥1.29 mM), reduced the nanoparticles’ hydrodynamic diameter (<500 nm) compared to media with lower lecithin concentrations. Furthermore, less than 10% of native digestive enzymes, like pepsin and pancreatin, adsorbed to the SPIONs. On the other hand, 40% of lactoferrin, a protein overexpressed in IBD [3], adsorbed to the surface of the nanoparticles.

By characterizing SPION behavior in simulated GIT fluids in vitro using IntesTiny, including IBD-specific environments, the physicochemical properties of orally administered nanoparticles can be engineered to achieve the desired diagnostic or therapeutic outcomes.

References
[1] S. Asad, A. C. Jacobsen, and A. Teleki, “Inorganic nanoparticles for oral drug delivery: opportunities, barriers, and future perspectives,” Dec. 01, 2022, Elsevier Ltd. doi: 10.1016/j.coche.2022.100869.
[2] M. Vertzoni et al., “Characterization of the ascending colon fluids in ulcerative colitis,” Pharm Res, vol. 27, no. 8, pp. 1620–1626, 2010, doi: 10.1007/s11095-010-0158-y.
[3] J. Dai, W. Z. Liu, Y. P. Zhao, Y. B. Hu, and Z. Z. Ge, “Relationship between fecal lactoferrin and inflammatory bowel disease,” Scand J Gastroenterol, vol. 42, no. 12, pp. 1440–1444, 2007, doi: 10.1080/00365520701427094.

Poster_P12_Yael Suarez