Thesis (M.S.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains xi, 133 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 129-133).

Low water solubility of drug compounds limits their dissolution in the aqueous body fluids. When formulated using conventional methods, those poorly water-soluble drugs often results in low and erratic bioavailability. The use of nanoparticle engineering technologies for the formulation of poorly water-soluble drugs is a valuable strategy to enhance dissolution rates and thus bioavailability. In Chapter 2, a nanoparticle engineering process, Evaporative Precipitation into Aqueous Solution (EPAS), was modified to provide improved control over the size of precipitated particles. The improved process, Advanced EPAS, was employed to prepare nanoparticles of the poorly water-soluble drug itraconazole (ITZ). The influence of processing parameters and formulation aspects on the size of suspended ITZ-particles was investigated. The process was shown to be robust such that the size distribution of dispersed nanoparticles was largely independent across the different parameters. In Chapter 3, aqueous nanoparticulate dispersions of the poorly soluble drug mefenamic acid (MFA) were developed and subsequently incorporated into controlled release formulations employing spray-drying. Release of MFA from spray-dried formulations was sustained and complete demonstrating the feasibility of using nanoparticulates for the preparation of controlled release systems. In Chapter 4, the nanoparticle engineering process, Rapid Freezing (RF), was utilized to produce nanostructured, amorphous aggregates of the poorly water soluble drug ketoprofen (RF-KET). The stability of RF-KET against recrystallization was improved through the deposition of a hydrophobic plasma-polymerized film. The coating presented an effective barrier against surface mobility and moisture uptake resulting in enhanced stability of RF-KET for up to six months at accelerated storage conditions as compared to three days for uncoated RF-KET. / text

The exploration of nanoparticles for applications in medicine has grown dramatically in recent years. Due to their size, nanoparticles provide an ideal platform for combining multiple functionalities and interfacing directly with the biological realm. Additionally, nanoparticles can have physical properties that don't naturally exist in biology. Metal nanoparticles in particular have unique optical and magnetic properties which have driven nanomaterials research. The optical properties of gold nanoparticles and the magnetic properties of iron nanoparticles make them suitable for use as contrast agents in diagnostics and for radiation enhancement in therapeutic applications. The strong optical absorption and scattering and the nature of the conduction electrons of gold particles makes them ideal contrast agents for two-photon microscopy, photoacoustic imaging, and photothermal therapy. The superparamagnetic nature of iron oxide nanoparticles is clearly visible in magnetic resonance imaging, rendering them suitable as whole-body imaging contrast agents. All nanoparticle types can serve as delivery vehicles for drugs consisting of small molecules, peptides, or nucleic acids. This multiplicity of characteristics renders nanoparticles suitable for use in combining diagnosis and therapy, such as using particles to first detect the spatial extent of a cancer, and then to enhance near-infrared radiation in the tissue optical window to induce localized heating of diseased tissue. This combined approach requires both a mechanism of enhanced imaging contrast and a localized therapeutic mechanism, and the studies presented in this dissertation present work both on these aspects. By coating iron oxide nanoparticle cores with gold shells, it is possible to obtain a nanoparticle with both magnetic and optical properties. While individual gold nanoparticles do not absorb light in the infrared, receptor-mediated aggregation and the plasmon coupling effect lead to enhanced optical absorption only in diseased tissue. In addition to exploring these advanced applications, this work presents a fundamental investigation into the stability of gold nanoparticles in biological media. A previously unknown mechanism of gold nanoparticle destabilization and opsonization is presented and supported, along with a technique for reducing this opsonization and greatly enhancing the stability of gold particles in biological applications. This work will provide guidance to future designs of nanoparticle systems. / text

Compared with traditional radioimmunoassay and fluoroimmunoassay for early diseases detection, the magnetic immunoassay utilizing magnetic nanoparticles as bio-labels and magnetic signal sensors as detectors has remarkable advantages because most biological samples exhibit no magnetic background and highly sensitive measurements can be performed. This thesis presents the development of biodetection platform taking advantage of the physical-and chemical-stability, low-toxicity, and environmentally-safety of magnetic iron oxide nanoparticles (IONPs) and the high-sensitivity, low-cost, and portable capabilities of magnetoresistive (MR) sensors. The first part explained why a magnetic biodetection platform is desirable, and what advantages it possesses. Then the magnetism of IONPs utilized in this detection system was introduced, followed by the introduction of main synthesis methods to obtain the desirable IONPs. The working principle of MR sensor was explained, and the recent advances about the biodetection platforms with various magnetoresistive sensors and magnetic IONPs labeling was reviewed. A brief summary of new contributions reported in this thesis was summarized. Then the establishment of home-made measurement setups for the characterization of MR sensor was described. The MR loops of MR sensors can be obtained with the instrument using two-point probe measurement, four-point probe measurement, or Wheatstone bridge measurement. The single MTJ sensor, MTJs array sensor, and the GMR spin valve sensor in Wheatstone bridge were characterized here. The magnetic IONPs were prepared through co-precipitation method and thermal decomposition method, and then surface-functionalized using citric acid and fatty acids to acquire carboxyl groups for the binding ability with biomolecules. The physical and chemical properties, sterilizing-treatment tolerability and biocompatibility of nanoparticles were studied. Furthermore, two new synthesis methods were developed to obtain novel magnetic gold/iron oxide nanocomposites for their potential use as magnetic bio-labels. A magnetic detection platform was built, and the detection of 10-nm superparamagnetic IONPs with MR sensor was first realized here. The output signal of the giant magnetoresistive (GMR) sensor in Wheatstone bridge exhibited log-linear function of the concentration of IONPs, making our sensing system suitable for use when ultra-small bio-labels are needed. The biodetection platform with MR sensor and IONPs was successfully developed and applied for the detection of antigen biomolecules. The feasibility of magnetic biodetection system, based on magnetic tunneling junction (MTJ) sensors and carboxyl-group functionalized IONPs, to detect AFP antigens (liver cancer biomarker) and p24 antigens (HIV biomarker) was demonstrated here for the first time. By taking advantages of its high sensitivity, low power consumption, low cost, and feasibility to be miniaturized, the development of magnetoresistive biodetection platform will bring revolutionary impact on the biodetection techniques for clinical early diseases diagnosis. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Silver nanoparticles (AgNPs) have gained much popularity in consumer products due to their strong antimicrobial ability. The majority of research concerning the biological effects of AgNPs has been limited to humans, mammals and freshwater organisms. Marine organisms, especially invertebrates, have been studied to a lesser extent. The objective of this thesis was to understand the effects of AgNPs on the marine benthic invertebrates. Specifically, we focused on the acute and sub-lethal toxicity of two AgNPs (Oleic acid coated AgNP (OAgNP) and Polyvinylpyrrolidone coated AgNP (PAgNP)) on marine invertebrate larvae across three phyla (i.e. the barnacle Balanus amphitrite, the limpet Crepidula onyx and the polychaete Hydroides elegans) in terms of mortality, growth, development and metamorphosis. Bioaccumulation and biodistribution of silver, as well as apoptosis induction were also investigated. To distinguish the toxic effects derived from nano-silver and aqueous form of silver, larvae were also exposed to silver nitrate (SN) in parallel. In the acute toxicity test, larvae were exposed to OAgNPs and PAgNPs for 48 hours, and the concentration leading to 10 % mortality (〖LC〗_10) were determined and compared. The results indicated that B. amphitrite and H. elegans were more sensitive to OAgNPs (〖LC〗_10: 0.138 and 2.63 × 〖10〗^(-4) μμg L-1, respectively) than PAgNPs (〖LC〗_10: 0.502 and 0.317 μμg L^(-1), respectively). In contrast, C. onyx was more susceptible to PAgNPs (LC10: 38.5 μμg L^(-1)) than OAgNPs (〖LC〗_10: 467 μμg L^(-1)). Among the three taxonomic groups, C. onyx was most tolerant of AgNPs, following by B. amphitrite and H. elegans. The sub-lethal effect of AgNPs resulted in a significant retardation in growth and development, and the reduction of settlement rate of all three species tested. In particular, the settlement rate of H. elegans was significantly lower in AgNPs treatment than in SN treatment, suggesting that toxicity of AgNPs might not be solely evoked by the release of silver ion (Ag+) into the test solution. The three species took up and accumulated silver efficiently from all forms. Importantly, AgNP aggregates were found along the digestive tract of C. onyx and the TEM images further confirmed that AgNPs were able to move across the plasma membrane. In addition, TUNEL assay indicated that AgNPs could induce apoptosis in B. amphitrite and C. onyx. In view of the very low number of detected apoptotic cells and the random occurrence of cell death found, AgNP-induced apoptosis does not appear to be the major toxicity mechanism in causing delayed growth and settlement failure. Unlike the results revealed from acute toxicity test, surface coatings did not affect the sub-lethal toxicity of AgNPs. This research clearly demonstrated that AgNPs exerted toxic effects in a speciesspecific manner, and long-term exposure of AgNPs might allow bioaccumulation of silver, induce apoptosis, and affect growth, development and recruitment of marine invertebrates. This study also highlighted the possibility that toxicity of AgNPs might be mediated through toxic Ag+ as well as the novel modalities of AgNPs. / published_or_final_version / Biological Sciences / Master / Master of Philosophy

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This dissertation describes the synthesis and characterization of nitrogen doped carbon nanotube (NCNT) supported nanoparticles for catalysis, specifically, the cathodic oxygen reduction reaction (ORR) in fuel cells. Strategies for synthesis of mono- and bimetallic nanoparticle catalysts through dendrimer based templating techniques and with the aid of metal organic chemical vapor deposition (MOCVD) precursors and efficient assembly protocols of the catalysts with the NCNTs are discussed in detail. Physicochemical properties of the NCNTs and NCNT supported catalysts were characterized using a host of tools including scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, x-ray photoelectron spectroscopy (XPS), thermo gravimetric analysis, BET surface area and pore size analysis and electrochemical techniques including cyclic voltammetry, chronocoulometry, chronoamperometry and rotating disk electrode voltammetry. Chapter 1 serves as a general introduction and provides a brief overview of challenges associated with the synthesis, characterization and utilization of graphitic carbons and graphitic carbon supported catalysts in heterogeneous catalysis. Chapter 2 provides an overview of the synthesis and characterization of systematically doped iron and nickel catalyzed NCNTs in an effort to understand the effect of nitrogen doping on ORR. Chapter 3 describes the use of NCNTs as supports for dendrimer templated nanoparticle catalysts for ORR. A facile synthetic strategy for the immersion based loading of catalysts onto NCNTs by spontaneous adsorption to achieve specific catalyst loadings is explored. Chapter 4 details the loading of monodisperse Pt, Pd and PtPd catalysts on the as synthesized NCNTs using MOCVD precursors. The MOCVD route offers promise for direct dispersion and activation of ORR catalysts on NCNT supports and eliminates a host of problems associated with traditional solvent based catalyst preparation schemes. Chapter 5 details future directions on a few topics of interest including efficient electrodeposition strategies for preparing NCNT supported catalysts, studies on PtCu catalysts for ORR and finally prospects of using NCNT supported catalysts in fuel cell applications.

Lignin is an undervalued product that does not yet provide economic returns. Finding value-added applications of lignin is needed to achieve economic sustainability. Carbon nanoparticles have great technological and industrial importance because of their enhanced physicochemical, electrical, thermal and mechanical properties. In this work a novel method has been explored to produce carbon nanoparticles from lignin. The objective of this work is to synthesize carbon nanoparticles with high surface area from lignin through the carbonization process. Lignin was dissolved in alkaline solutions with different weight ratios of lignin and potassium hydroxide. An intermediate sublimation process was adopted to reduce agglomeration of particles. The lignin was thermo-stabilized after the sublimation process in oxidizing atmosphere followed by the carbonization process in an inert atmosphere at 700oC using tubular furnace. The increase in glass transition tem-perature during thermo-stabilization process was confirmed by DSC analysis. The con-densation reactions during thermo-stabilization process were confirmed by FTIR analysis. The formation of carbon nanoparticles was confirmed by transmission electron microscopy (TEM) analysis. Carbon nanoparticles with high specific surface area of 42 m2/g were produced. From the DLS particle size distribution it was found that 5 wt% KOH is the optimum concentration for synthesizing carbon nanoparticles from lignin. / Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA) New Directions Research Program for funding the project (number SR 225).

Adenosine is currently limited in its application as a treatment for various cancers since intravenous infusion has not been successful due to enzymatic degradation. Entrapment/association of adenosine into chitosan nanoparticles offers a possible solution to this problem. Chitosan nanoparticles which are formed by ionotropic gelation. The size, zeta potential, morphology, entrapment efficiency, and in vitro drug release were investigated. In the swollen state, nanoparticle had an average size between 425 to 515 nm and a positive zeta potential, as measured by dynamic light scattering. Particle size measured by transition electron microscopy varied between 135 to 183 nm. Average entrapment efficiency in the range of 72 to 78% was achieved depending on initial adenosine loading and an average association efficiency of 84%. Release studies show that more than 98% of the adenosine remained entrapped/associated with the chitosan nanoparticles for at least 120 hours in PBS (pH 7.4).