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

药物溶解度一直是药理学家的终极追求，并且代表了降低医疗成本的高度期望的目标。药物制剂与其给药途径密切相关。一些药物由于其化学不稳定性、毒性和代谢途径的普遍性而从未上市，它们的药理学益处在大手术之前仍未被利用，例如一氧化氮（NO）。已经提出了许多策略来抵消溶解度差的问题，例如使用含有药物的聚合物支架，但由于其未知的降解动力学，任何定制药物剂量测定的尝试都受到阻碍。为了使药物真正发挥其治疗作用，还必须克服另外两个挑战：靶向和控释。靶向特定的细胞群减少了全身性的副作用;因此将新的医疗应用扩展到无数的患者类别，这些患者的治疗，使用特别有毒的化学品，迄今为止是不可能的。这样的例子是对老年患者、新生儿和婴儿施用麻醉剂。控制释放将确保药物持续存在可证明的治疗效果所需的时间。在这个项目中，我们试图证明肺部给药的治疗性气体药物结合到超顺磁性纳米粒子，可以磁靶向的可行性;药物必须以适当的速度，在适当的时间内，纳米粒子必须不存在健康风险。我们通过将气体NO与功能化的Fe 3 O 4纳米颗粒（FDA批准）化学结合来实现这一点，然后将其加载到亚微米尺寸的聚合物颗粒中，这些颗粒足够大，可以通过气道进入肺部深处，以释放NO。磁场用于将颗粒靶向肺壁，以保持它们在那里的存在，持续较长的治疗时间。这将是一个两部分研究计划的可行性研究，涉及纳米颗粒功能化和亚微米级壳聚糖颗粒的形成。第二部分将涉及到动物模型和监测的交付。

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.