Cellular Drug Delivery

Patricia Müller (master student), Joram Kuropka (Erasmus student), Foteini Tzioufa (PhD student), Dinh Son Vo (PhD student), Xiguo He (PhD student) and Madlen Hubert (PI). Professor Emeritus Per Artursson (not in picture).

A nanosized drug delivery platform for enhanced antibiotic absorption

Oral antibiotics offer a convenient and cost-effective alternative to intravenous treatments, but many suffer from poor solubility, low stability in the gastrointestinal tract, and limited absorption. This not only reduces efficacy but also contributes to antibiotic resistance and gut microbiota disruption.

Our research focuses on developing nanocarrier-based drug delivery systems that improve antibiotic absorption by enhancing solubility, stability, and targeted delivery. By designing structured lipid nanoparticles, we aim to transport antibiotics efficiently to the intestinal epithelium for optimal uptake. These nanocarriers are engineered to withstand the harsh gastrointestinal environment while maximizing membrane permeability.

Through a combination of nanotechnology, digestion-permeation assays, and mechanistic cell studies, we explore the molecular interactions driving absorption. Our goal is to create innovative solutions that improve antibiotic effectiveness while minimizing unwanted side effects, ultimately advancing oral drug delivery for global healthcare.

Advancing drug absorption studies with human intestinal organoids

We use innovative 3D human intestinal organoid models to enhance drug absorption predictions and advance oral drug delivery research. Unlike conventional cell-based models, organoids replicate the structure and function of the intestinal epithelium, making them a powerful tool for studying drug transport and targeted therapies for gastrointestinal diseases like inflammatory bowel disease.

3D intestinal organoids by isolating stem cell-containing crypts from different human tissue. 3D organoids are derived from these crypts as basal-out cultures (which faces the lumen in vivo) in an extracellular matrix scaffold (Matrigel) with appropriate growth factors. To study drug uptake at the apical surface, organoid polarity can be reversed by removing the extracellular matrix, creating apical-out organoids in suspension. These models retain their ability to differentiate into various intestinal epithelial cell types and maintain barrier function, making them ideal for oral drug delivery studies.

By providing a more reliable and translationally relevant platform, 3D organoids improve disease modeling and therapy development. Using patient-derived organoids, we aim to refine drug uptake predictions and explore intracellular delivery of novel drug modalities, including nanoparticle-based treatments. Our research bridges the gap between laboratory studies and clinical application, paving the way for more effective and personalized therapies.

If you want to learn more about opportunities for thesis projects or long-term positions in the Cellular Drug Delivery group, please send your inquiry, including your CV, to madlen.hubert@uu.se

Selected publications:

1. He X, Karlsson PA, Xiong R, Moodie LWK, Wang H, Bergström CAS, Hubert M*. Liquid crystal nanoparticles for oral combination antibiotic therapies: A strategy towards protecting commensal gut bacteria during treatment, Journal of Colloid and Interface Science, 2025, 678, 287-300. https://doi.org/10.1016/j.jcis.2024.08.230.
2. Ceylan M, Tzioufa F, Di Martino ML, Hammar R, Lopes ACC, Eriksson J, Vo DS, Sundbom M, Skogar M, Hellström PM, Webb DL, Karlgren M, Gardner I, Lundquist P, Hjelmqvist D, Sellin ME, Hubert M* and Artursson P*. Human jejunal enteroids for studies of epithelial drug transport and metabolism, bioRxiv, 2025, https://doi.org/10.1101/2025.03.17.643545.
3. Rodrigues L, Schneider F, Zhang X, Larsson E, Moodie LWK, Dietz H, Papadakis CM, Winter G, Lundmark R, Hubert M*. Cellular uptake of self-assembled phytantriol-based hexosomes is independent of major endocytic machineries, Journal of Colloid and Interface Science, 2019, 553, 820-833. https://doi.org/10.1016/j.jcis.2019.06.045.
4. Rodrigues L, Raftopoulos K, Tandrup Schmidt S, Schneider F, Dietz H, Rades T, Franzyk H, Pedersen AE, Papadakis CM, Christensen D, Foged C, Winter G and Hubert M*. Immune responses induced by nano-self-assembled lipid adjuvants based on a monomycoloyl glycerol analogue after vaccination with the Chlamydia trachomatis major outer membrane protein, Journal of Controlled Release, 2018, 285, 12-22. https://doi.org/10.1016/j.jconrel.2018.06.028.
5. Rodrigues L, Kyriakos K, Schneider F, Dietz H, Papadakis CM, Winter G and Hubert M*. Characterization of lipid-based hexosomes as versatile vaccine carriers, Molecular Pharmaceutics, 2016, 13 (11), 3945-3954. https://doi.org/10.1021/acs.molpharmaceut.6b00716.