THE PHARMACOKINETICS OF METAL- BASED ENGINEERED NANOMATERIALS, FOCUSING ON THE BLOOD-BRAIN BARRIER

摘要: OF DISSERTATION THE PHARMACOKINETICS METAL-BASED ENGINEERED NANOMATERIALS, FOCUSING ON BLOOD-BRAIN BARRIER Metal-based engineered nanomaterials (ENMs) have potential to revolutionize diagnosis, drug delivery and manufactured products, leading greater human ENM exposure. It is crucial understand pharmacokinetics their association with biological barriers such as the blood-brain barrier (BBB). Physicochemical parameters size surface modification of ENMs play an important role in fate, including brain association. Multifunctional showed advantages across highly regulated BBB. There are limited reports on distribution among blood vasculature, BBB, parenchyma. In this study, ceria was used study effect its pharmacokinetics. Four sizes were studied. Five nm a longer half-life higher compared other 15 30 had cell than 5 or 55 ceria. Because long circulation high sizes, between BBB parenchyma The situ perfusion technique (99%) luminal rather For biomedical applications central nervous system (CNS), it vital develop stable biocompatible enhance uptake by taking advantage unique properties. Cross-linked nanoassemblies entrapping iron oxide nanoparticles (CNA-IONPs) controlled particle conditions less toxicity comparison Citrate-IONPs. CNA-IONPs considerably enhanced MRI T2 relaxivities generated heat at mild hyperthermic temperatures (40 ~ 42°C) presence alternating magnetic field (AMF). Numerous researchers whole body hyperthermia can increase permeability for therapeutic application. Compared conventional hyperthermia, AMF-induced increased shorter duration lower temperature, providing IONP flux reduced toxicity. Overall, optimized physicochemical properties into desirable pharmacokinetics, which provide great diagnosis therapy CNS.