Our foil-type devices show great potential for delivering poorly permeable macromolecules by enabling unidirectional release of the loaded pharmaceutical composition near the epithelium in the small intestine or colon. The foil devices have shown great potential for delivering peptides, with a significant increase in the absorption of solid insulin dosage by ∼12 times and nisin by ∼4 times in rats and pigs, respectively. (Mahdi Ghavami et al., Journal of Controlled Release, 2023).
The foils are loaded with a solid-state formulation containing the active pharmaceutical ingredient and then coated and rolled into enteric capsules. The coated lid must remain intact to ensure drug protection in the rolled state until the targeted release in the small intestine after capsule disintegration. We have done a study to compare different mixtures of enteric polymers and a plasticizer, PEG 6000, as potential coating materials. We evaluated mechanical properties as well as drug protection and targeted release in gastric and intestinal media, respectively. Commercially available Eudragit® FL30D-55 is the most suitable material due to its high strain at failure and integrity after capsule fitting. In vitro studies of coated foils in gastric and intestinal media confirmed successful pH-triggered drug release (Carmen Milan-Guimera et al., Pharmaceutics, 2024).
To visualize the behaviors of our devices in animal studies we have explored how to magnetically and/or radiopaque functionalize the foils by adding BaSO4 or Fe3O4 nanoparticles. The resulting foils have been characterized by surface characterization, mechanical testing, and X-ray imaging. Unfolding of the foil and its very close proximity to the small intestine can be observed 2 h post-administration by applying both computed tomography scanning and planar X-ray imaging (Rolf Bech Kjeldsen et al, ACS Biomaterials Science and Engineering, 2023).
One of the primary concerns associated with the use of our foil-type devices so far has been the utilization of nonbiodegradable elastomers (PDMS) in the fabrication of the devices. Therefore, we have synthesized a biodegradable elastomer, polyoctanediol citrate (POC), via a one-pot reaction, with subsequent purification and microscale pattern replication via casting. The microstructure geometry was designed to enable fabrication of foil-type devices with the selected elastomer, which has a high intrinsic surface free energy. The realized foil devices have been tested for drug release and show promising properties based on mechanical testing, and degradation studies (Reece McCabe et al., ACS Applied Biomaterials, 2024).
To get closer to the epithelium, we are exploring micromotors loaded into the foil structure. We are following an approach where microcontainers are loaded with magnesium micromotors and coated with a pH-responsive lid (Tijana Maric et al., Small 2023). We also explore needle shaped micromotors to be ejected from the foil. We additionally study delivery of a variety of new ‘cargos’. One of these is so-called polymersomes, that can be loaded with drugs and where the release can be triggered by e.g oxygen content. In a recent study, we explored a novel approach using oxygen-producing enzymatic reactions within biodegradable PEG-p(CL-g-TMC) polymersomes to modulate drug release. These polymersomes enhance the release of hydrophobic drugs while retaining hydrophilic drugs (Matteo Tollemeto et al, Angewandte Chemie, 2024).
