NSERC/MRI, guided delivery and controlled release of core/shell superparamagnetic nanoparticle-based submicron-sized respiratory and systemic drug carriers

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Drug solubility continues to be an ultimate pursuit of pharmacological scientists, and represents a highly desirable aim for health care cost reduction. Drug formulations are intimately connected to the pathway of their administration. Some drugs have never been marketed, due to their chemical instabilities, toxicities and the ubiquities of their metabolic pathways, their pharmacological benefits remaining unexploited, prior to major surgeries, such as nitric oxide (NO), are cases in point. Many strategies have been suggested to counteract the poor solubility problem, such as the use of polymeric scaffolds containing the drugs, but due to their unknown degradation kinetics, any attempts at tailoring drug dosimetry are hindered. Two further challenges will have to be overcome for the drug to truly fulfill its therapeutic effects: targeting and controlled release. The targeting of specific cell populations reduces systemic side effects; hence extending new medical applications to a myriad of patient categories, whose treatments, using particularly toxic chemicals, have so far been impossible. Such an example is the administration of anesthetics to elderly patients, neonates and infants. Controlled release would assure the continual presence of the drug for periods necessary for demonstrable therapeutic effects. In this project, we seek to demonstrate the feasibility of the pulmonary administration of therapeutic gaseous drugs bound to superparamagnetic nanoparticles that can be magnetically targeted; the drug must be delivered at an appropriate rate, for an appropriate period of time, and the nanoparticles must not present health risks. We do this by chemically binding the gas NO to functionalized Fe3O4 nanoparticles (FDA approved) that will then be loaded into submicron-sized polymer particles large enough to pass through the airway, into the deep lungs, to release the NO. Magnetic fields serve to target the particles to the lung walls, to maintain their presence there for long therapeutic periods. This will be the feasibility study of a two parts research programme, having to do with nanoparticle functionalization and the formation of submicron-sized chitosan particles. The second part will concern delivery into animal models and monitoring.