Study of lipid based nanoparticles as carriers for anticancer ruthenium metallodrugs

Abstract

Ruthenium compounds have received great attention in the field of metallodrugs because of their potential as anticancer agents. Complexes containing Ru2(II,III) dimetal cores coordinated to non-steroidal anti-inflammatory drugs (NSAIDs) developed in our research group have shown promising results in studies in vitro and in vivo in glioma models, such as the glioblastoma multiforme, a highly malignant brain cancer. The main objective of this proposal for Sandwich stage is to investigate the feasibility of developing hybrid nanoparticle lipid systems with Ru2(II,III)-NSAID complexes aiming to promote loading and sustained release of the metallodrugs in the brain. Lipid nanoparticles developed by Dr. Wu's group, such as lipid-terpolymer nanoparticles, were found to be capable of crossing the blood brain barrier, thus showing potential for treatment of gliomas, and allowing, among other things, to increase the intracellular and intratumor bioavailability and to decrease the systemic toxicity of antitumor drugs. In this context, the main goals of this research plan are: 1) to develop methodology for preparation of lipid nanoparticles, as Solid Lipid Nanoparticles (SLNs) and lipid-terpolymer nanoparticles, containing the metallodrugs; 2) to characterize the hybrid nanoparticles by diverse techniques; 3) to investigate the feasibility of releasing the metallodrugs from the hybrid materials; 4) to perform studies in vitro in order to verify the potential application of the new systems in anticancer treatments. (AU)