| Abstract: | Delivering specific bioactive agents with sufficient bioavailability to the targeted brain area across blood brain barrier (BBB) remains a big challenge. Nanoparticle (NP)-based drug-carrier systems have been reported to aid in retention and specific delivery of a multitude of potential therapeutic agents due to their excellent tunable surface functionality. Magnetic NPs, in particular, have earned interest because of their unique properties to respond to magnetic fields, and demonstrated their potential for controlled drug delivery. However, the dynamic transport of these NPs inside each individual⁰́₉s brain vasculature has not yet been well understood and their controllability is hindered by low magnetic driving forces. Addressing this is a critical step forward to controlled drug delivery for non-invasive brain therapeutics. In this dissertation, the motion of magnetic NPs insides the brain vasculature is studied by using Newton⁰́₉s law and advection-diffusion equations. The patient-specific transport path of NPs is designed based on the reconstructed vascular model, and then the external magnetic field required to drive these NPs can be calculated. Physiologically based pharmacokinetic (PBPK) modeling is further developed to explore the biodistribution of intraperitoneal (IP) injected of superparamagnetic iron oxide nanoparticles coated by gold and conjugated with poly (ethylene glycol) (PEG) (SPIO-Au-PEG NPs) in mice. In vivo experiment is then carried out to study the targeting efficiency and verify the PBPK. To better control the magnetic NPs and increase the targeting efficiency, different shapes of biodegradable hydrogel microrobots containing SPIO NPs are designed and 3D-printed. A theoretical analysis of the motion of the microrobots and experimental verification were carried out. The theoretical modeling, numerical simulation and experimental validation described in this dissertation lay solid foundation towards non-invasive brain therapeutics with maximal accuracy and minimal side effects. The electronic version of this dissertation is accessible from https://hdl.handle.net/1969.1/197838 |
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