Advanced analytical strategies to determine biomedical parameters for medical diagnostics, drug delivery, and therapy

Abstract

Biomedical parameters are critical for diseases prognosis, diagnosis and therapy. Many research groups have dedicated their studies to develop analytical instrumentation and apply analytical methods to determine biomedical parameters that have the potential to help with disease control and increase public health. This dissertation focuses on three major aspects of analytical strategies development and applications: 1) detection of pH changes caused by nanotoxicity (induced by TiO2 nanoparticles) using newly developed micro-pH sensor, 2) quantification of renal cell carcinoma (RCC) biomarkers by high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS), and 3) nuclear magnetic resonance (NMR) studies of porous wall hollow glass microspheres (PWHGMs) that have the potential to be used as drug delivery carriers. Firstly, a dual-core fiber-optic pH micro-probe was developed which can be used within the biologically relevant pH range from 6.20 - 7.92 (R2 = 0.9834). Secondly, a targeted HPLC-MS/MS protocol was developed to simultaneously monitor four urinary biomarkers for RCC and applied to human urine specimen analysis. Thirdly, a vacuum-based loading system was developed to charge PWHGMs with specific materials followed by a washing procedure. Immiscible binary model systems (n-dodecane/water and chloroform/water) as well as isopropanol- acetic acid esterification and the hydrolysis of isopropyl acetate were investigated to obtain NMR evidence for material loading into PWHGMs and their subsequent release into the surrounding solutions. In addition, microspheres loaded with H2O were suspended in D2O to obtain quantitative information about the release kinetics from PWHGMs. The results demonstrate that NMR is a particularly useful tool to study developments and applications of PWHGMs in the targeted and controlled drug delivery --Abstract, page iv