Synthesis of functionalized magnetic nanosystems:

Develop a protocol to produce GMP-grade PEG-coated magnetic nanoparticles and use these nanoparticles to demonstrate the feasibility for magnetically driven drug targeting.

The goal will be to develop a precise process control to avoid variability in particle core size and PEG coating thickness and produce coated nanoparticles with controlled dimensions and a diameter of about 150 nm.

At the end of the project more than 10 different fully characterized MIONs concerning physical, chemical and properties will be available for application.

The previous nanoparticle synthesis approach was suitable for exploratory research projects; it does not conform to Current Good Manufacturing Practice (CGMP) standards and is not amenable to scale-up, which are critical barriers against progressing toward clinical trials.

The stent produced for this aim (magnetic stent and non-magnetic stent) have separately met key ISO 10933 biocompatibility and non-cytotoxicity criteria.

Ex-vivo investigations:

We will test 3 magnetic stent-grafts and 3 non-magnetic control stent-grafts for their ability to capture the PEG-coated magnetoresponsive nanoparticle clusters with different particle sizes, shapes, and PEG thickness. We will expose the implanted stents to a suspension of PEG-coated nanocomposites at a concentration of approximately 1.0×10⁶ particles/mL. Image analysis software will quantify particle capture rate for captured particle density at selected time points (magnetic nanoparticle will circulate in the umbilical artery for 10, 20, 30 minute). A rate of ≥ 200,000 particle captured/cm² will be considered successful, based on optimal endothelial cell seeding conditions (for magnetic field gradient range between 0.2 to 0.6T). The mean percent stent coverage with functionalized magnetic clusters will be presented with 95% confidence intervals assuming a t-distribution. A two-sample t-test will compare differences between the particle coverage of the magnetic and the non-magnetic stent to determine statistically significant differences. Challenge: possible sub-optimal outcomes include inadequate stent apposition to the artery wall.

To assess the ability of these coupled technologies for safety and efficacy in control, as well as rapid endothelialisation of implanted stent.

At least one MION system will be transferred to a GMP pilot production line.

The human umbilical artery will be isolated from freshly collected umbilical cords (kindly provided by the Department of Gynecology, University Hospital “Pius Branzeu” Timisoara). The study protocol is already approved by the responsible authority from the University Hospital.