OncoNanoBBB

Current treatment options for brain cancer are limited with patients having a poor prognosis. One of the major hurdles is the blood brain barrier (BBB) which prevents effective doses of drugs reaching the site of disease. There is thus a major need for technologies that can successfully overcome such a hurdle without having a negative effect on safety and tolerability. The use of nanoparticles (NPs) to deliver drugs to the brain by infiltrating BBB may provide a significant strategy to drug delivery. The primary advantage of nanoparticle carrier technology is that it can cross blood brain barrier entrapping the original characteristics of the therapeutic drug molecule.

Furthermore, such a system may reduce drug leaching in the brain and decrease peripheral toxicity. The in vivo assessment of nanoparticles fate introduces the need of advanced molecular imaging technologies. In the frame work of OncoNanoBBB project the partners from Industry and Academia work together on the problem of delivering therapeutic agents, e.g. for brain cancer, across the blood-brain barrier (BBB) at the efficacious dose and use the advanced imaging techniques for its assessment.

The main scientific objectives of OncoNanoBBB are the design and synthesis of a range of nanoparticles (NPs), suitable for drug delivery across BBB, as well as developing efficient in vivo imaging technique. OncoNanoBBB researchers aimed to optimise the NPs formulation for using a variety of pharmaceutical excipients and determine the mechanism of action of the technology for penetrating the BBB.

Besides its scientific objectives, OncoNanoBBB will provide a framework for cooperation and knowledge sharing between a pharmaceutical industry and two academic institutions in UK and Greece with complementary expertise in project objectives, as well as dissemination of project outcomes.

Novel nanoparticles modified with glucose moieties were designed and assessed. Nanoparticles were radiolabelled using well tested SPECT radioisotopes and imaged in vivo with high resolution imaging systems. This molecular imaging technique allows the acquisition of spatiotemporal information on nanoparticles biodistribution, while minimising the number of required animals and increasing accuracy.

Optimisation of the existing imaging systems was carried out, to allow efficient brain imaging. Imaging protocols were designed and evaluated. We believe this novel technology will be a unique drug discovery tool with the potential to enhance efficacy of established agents, reduce systemic exposure of the chemotherapeutic agent, thus minimising both the on/off-target toxicity through enhancement of drug absorption at the target site.

E.A. Fragogeorgi, I. N. Savina, T. Tsotakos, E. K Efthimiadou, S. Xanthopoulos, L. Palamaris, D. Psimadas, G. Kordas, S. Mikhalovsky, M.d Alavijeh, G. Loudos, "Comparative In vitro Stability and Scintigraphic Imaging for Trafficking and Tumour Targeting of a Directly and a Novel 99mTc(I)(CO)3 Labelled Liposome" International Journal of Pharmaceutics, 2014.