Magnetic nanoparticles for hyperthermia-triggered drug release
Advanced theranostic concepts involving the use of iron oxide nanoparticles continue to be of prime interest for biomedical applications due to the many beneficial properties of this material. We produce superparamagnetic iron oxide nanoparticles (SPION) using our enclosed flame reactor. The crystallinity of the the in situ flame-coated product SPION can be finely tuned and most importantly, the magnetic properties are not affected by the nanothin SiO2 coating. In fact, the silica coating improves magnetic hyperthermia to reach clinically relevant values and the nanoparticles are viable as MRI contrast agents with a relaxivity rate comparable to that of commercial inorganic MRI agents. We are currently developing site-specific, stimuli-responsive oral drug delivery systems carrying biological drugs using our flame-made SPION. These nanoparticles can generate a rapid local temperature increase in the presence of an alternating magnetic field, which can be used to trigger drug release.
Teleki, A., F.L. Haufe, A.M. Hirt, S.E. Pratsinis, and G.A. Sotiriou, “Highly scalable production of uniformly-coated superparamagnetic nanoparticles for triggered drug release from alginate hydrogels,” RSC Adv. 6, 21503-21510 (2016).
Sotiriou, G.A., M.A. Visbal-Onufrak, A. Teleki, E.J. Juan, A.M. Hirt, S.E. Pratsinis, and C. Rinaldi, “Thermal energy dissipation by SiO2-coated plasmonic-superparamagnetic nanoparticles in alternating magnetic fields,” Chem. Mater. 25, 4603-4612 (2013).
On demand drug amorphization
Poor aqueous drug solubility represents a major challenge in oral drug delivery. A novel approach to overcome this challenge is drug amorphization inside a tablet, i.e. on-demand drug amorphization. We study the incorporation of functional nanoparticles into tablets to achieve on-demand drug amorphization. We use photothermal plasmonic nanoparticles in tablets with a crystalline drug and a polymer. As the tablets are irradiated with a laser, the plasmonic nanoparticles homogeneously heat the tablet and the temperature increase is correlated to the rate and degree of amorphization. Furthermore, we use superparamagnetic nanoparticles to induce amorphization in tablets exposed to an alternating magnetic field. This work is carried out in collaboration with Prof. Korbinian Löbmann at the University of Copenhagen.
Lipid-based formulations for oral peptide delivery
Oral delivery of hydrophilic macromolecules such as peptides remains a major challenge to formulation scientists due to their inherent poor stability in the gut as well as their low intestinal permeability. Thus, current oral peptide dosage forms suffer from very poor bioavailability and high patient variability. Several strategies have been proposed to overcome these hurdles including the use of transient permeation enhancers (TPEs) such as medium chain fatty acids and self-emulsifying drug delivery systems (SEDDs). We develop SEDDs-based peptide formulations that incorporate lipid excipients. The digestion of these lipid excipients will generate fatty acids that will act as TPEs. This will result in continuous and simultaneous release of TPEs and peptide at high concentrations to the intestinal wall. The project thus aims to systematically design functional peptide formulations to gain mechanistic understanding of the interplay of lipid excipients, peptides and physiological conditions in the intestine. The project is part of SweDeliver and is carried out in close collaboration with Prof. Christel Bergström at Uppsala University using the in vitro digestion-permeation device established there.