Browsing Theses and Dissertations School of Pharmacy by Title "From Nanoparticles to Zinc Finger Proteins to Electronic Nicotine Delivery Systems: The Clinical and Biomolecular Evaluation of Potentially Toxic Heavy Metals"
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From Nanoparticles to Zinc Finger Proteins to Electronic Nicotine Delivery Systems: The Clinical and Biomolecular Evaluation of Potentially Toxic Heavy MetalsPhysicochemical Properties of Sodium Ferric Gluconate There are concerns that differences in iron release between brand sodium ferric gluconate (SFG) (Ferrlecit) and generic SFG (generic SFG) intravenous (IV) iron nanoparticle drugs, which are used to treat chronic kidney disease can be caused by differences in the products’ physicochemical properties. However, a standardized, SFG product specific, physicochemical measurement regulatory guidance is not available. Iron core measurements including optical spectroscopy, ICP-MS, XRPD, 57Fe Mössbauer spectroscopy, and XAS, found both products’ cores to be similar ferric-iron-oxide structures. Measurements focused on the carbohydrate shell including forced acid degradation, concentration dependent DLS, AUC, and GPC found differences in particle size, acid stability/iron lability, and molecular weight distribution, that may impact iron release. Cadmium Targeting of Tristetraprolin Zinc finger (ZF) proteins regulate inflammation and are a potential target for cadmium. Zinc bound double Cys3His domain ZF protein tristetraprolin (TTP) regulates inflammation by binding to AU-rich cytokine mRNA. Using a TTP peptide (TTP-2D), Zn2-TTP-2D, cadmium was observed to displace Zn in a concentration dependent manner by spin-filter/ICP-MS coupled to native ESI-MS. Cadmium was also found to displace zinc from RNA bound Zn2-TTP-2D complex (Zn2-TTP-2D/RNA) by ESI in a concentration dependent manner, resulting in Cd1Zn1-TTP-2D/RNA and Cd2-TTP-2D/RNA complexes. Using fluorescence anisotropy cadmium displacement of zinc from Zn2-TTP-2D/RNA complex did not disrupt RNA binding. E-Cig E-liquid Matrix’s Effect on Metal Aerosolization Potentially toxic levels of metals, such as chromium, nickel, copper, and lead, have been reported in e-liquids (liquids composed primarily of a mixture of propylene glycol (PG), glycerol (G)) and nicotine, and generated aerosols of electronic nicotine delivery systems (ENDS). However, the variables that affect metal transfer from the e-liquid to the aerosols are unknown. Using a custom ENDS aerosolization device and aerosolization approach, following CORESTA 81 guidance, the aerosolization of metal spiked model e-liquids (PG and G) were measured. Using ICP-MS to measure aerosol metal content to determine the effect of e-liquid on chromium, nickel, copper, and lead, it was found that all four metals are more readily aerosolized in PG dominant e-liquids than G dominant e-liquids.