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Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known. The goals of this dissertation work were (a) to determine the energetics of interactions between HPMC and model surfactants and the extent to which these solution-state interactions modulate the adsorption of these excipients onto solid surfaces, (b) to determine and characterize the structures of various aggregate species formed by the interaction between hydroxypropyl methylcellulose (HPMC) and model surfactants (nonionic and ionic) in solution-state, and (c) to extend these quantitative relationships to interpret probable mechanisms of mixed adsorption of excipients onto the model NDDS surface. A unique approach utilizing fluorescence, solution calorimetry and adsorption isotherms was applied to tease apart the effect of solution state interactions of polymer and surfactant on the extent of simultaneous adsorption of the two excipients on a model surface. The onset of aggregation and changes in aggregate structures were quantified by a fluorescence probe approach with successive addition of surfactant. In the presence of HPMC, the structures of the aggregates formed were much smaller with an aggregation number (Nagg) of 34 as compared to micelles (Nagg ~ 68) formed in the absence of HPMC. The strength of polymer-surfactant interactions was determined to be a function of ionic strength and hydrophobicity of surfactant. The nature of these structures was characterized using their solubilization power for a hydrophobic probe molecule. This was determined to be approximately 35% higher in the polymer-surfactant aggregates as compared to micelles alone and was attributed to a significant increase in the number of aggregates formed and the increased hydrophobic microenvironment within these aggregates at a given concentration of surfactant. The energetics of the adsorption of SDS, HPMC, and SDS-HPMC aggregate onto nanosuspensions of silica, which is the model solid surface were quantified. A strong adsorption enthalpy of 1.25 kJ/mol was determined for SDS adsorption onto silica in the presence of HPMC as compared to the negligible adsorption enthalpy of 0.1 kJ/mol for SDS alone on the silica surface. The solution depletion and HPMC/ELSD methods showed a marked increase in the adsorption of SDS onto silica in the presence of HPMC. However, at high SDS concentrations, a significant decrease in the adsorbed amount of HPMC onto silica was determined. This was further corroborated by the adsorption enthalpy that showed that the silica-HPMC-SDS aggregation process became less endothermic upon addition of SDS. This suggested that the decrease in adsorption of HPMC onto silica at high SDS concentrations was due to competitive adsorption of SDS-HPMC aggregates wherein SDS is displaced/desorbed from silica in the presence of HPMC. At low SDS concentrations, an increase in adsorption of SDS was due to cooperative adsorption wherein SDS is preferentially adsorbed onto silica in the presence of HPMC. This adsorption behavior confirmed the hypothesis that the solution-state interactions between pharmaceutical excipients such as polymers and surfactants would significantly impact the affinity and capacity of adsorption of these excipients on NDDS surfaces.

An aqueous nanoparticle dispersion is a complex fluid whose mobility in porous media is controlled by four key factors: the conditions necessary for the stability of nanoparticle dispersions, the kinetics of nanoparticle aggregation in an unstable suspension, the rheology of stable or unstable suspensions, and the interactions between the nanoparticles and oil/water interface and mineral surfaces. The challenges in controlling nanoparticle transport come from the variations of pH and ionic strength of brine, the presence of stationary and mobile phases (minerals, oil, water and gas), the geochemical complexity of reservoir rocks, and pore-network. The overall objective of this work is to achieve a better understanding of nanoparticle transport in porous media based on a systematic experimental and theoretical study of above factors. For this purpose, the critical conditions for the aqueous stability of nanoparticles are identified and fit by a theoretical model, which describes the interaction energy between silica nanoparticles. Above critical conditions nanoparticle aggregation becomes significant. A model for the aggregation kinetics is developed and validated by experiments. A mechanistic model for predicting the viscosity of stable and unstable silica nanoparticle dispersions over a wide range of solid volume fraction is developed. This model is based on the concept of effective maximum packing fraction. Adsorption experiments with silica nanoparticles onto quartz, calcite and clay surfaces and interfacial tension measurements provide insightful information on the interaction of the nanoparticles with minerals and decane/water interface. The extent of nanoparticle adsorption on mineral/water and decane/water interfaces is evaluated based on DLVO theory and Gibbs’ equation. Visual observations and analytical methods are used to understand the interaction of nanoparticles with clay. The characterization of nanoparticle behavior in bulk phases is built into an understanding of nanoparticle transport in porous media. In particular, the rheology of nanoparticle dispersions flowing through permeable media is compared with those determined using a rheometer. In the presence of residual oil, the retention of silica nanoparticles at water/oil interface during steady flow is investigated. The results from batch experiments of nanoparticle adsorption are used to explain the flow behavior of these nanoparticles in a glass bead pack at residual oil saturation. / text

Microbial resistance to the current available antibiotics is considered a global health problem, especially for the Multi-Drug Resistant pathogens (MDR) including methicillin resistant Staphylococcus aureus. Recently nanoparticles (NPs) have been involved in variety of antimicrobial applications due to their unique properties of antibacterial effects. However, the molecular mechanisms behind their antibacterial activity are still not fully understood. In this study, we produced silver Ag NPs (average size 27 nm) and silver-Titanium Ag-TiO2 NPs (average size 47 nm) using picosecond laser ablation. Our results showed that both laser NPs had obvious size-dependent antibacterial activity. The laser Ag NPs with a size of 19 nm and Ag-TiO2 NPs with a size 20 nm presented the highest bactericidal effect. The laser generated Ag and Ag-TiO2 NPs with concentrations 20, 30, 40, and 50 Î1⁄4g/ml showed strong antibacterial effect against three bacterial strains: E. coli, P. aeruginosa, and S. aureus, and induced the generation of reactive oxygen species (ROS), lead to cell membrane interruption, lipid peroxidation, DNA damages, glutathione depletion and the eventual cell death. Both types of laser NPs at two concentrations (2.5 and 20 Î1⁄4g/ml) showed low cytotoxicity to the in vitro cultured five types of human cells originated from the lung (A549), kidney (HEK293), Liver (HepG2), skin (HDFc) and blood vessel cells (hCAECs). The antibacterial activity of the laser generated Ag and Ag-TiO2 NPs had lasted for over one year depending on the degree of air exposure and storage conditions. Frequent air exposure increased particle oxidation and reduced the antibacterial durability of the laser generated Ag NPs. The laser generated Ag NPs had lower antibacterial activity when stored in cold compared to that stored at room temperature. The antibacterial activity of laser generated Ag and Ag-TiO2 NPs were also compared with four types of commercial based-silver wound dressings (Acticoat TM, Aquacel® Ag, Contreet ®Foam, and Urgotul® SSD) against E. coli to inform future application in this area. In conclusion, laser generated Ag and Ag-TiO2 NPs have strong bactericidal effect and low toxicity to human cells which could be a type of promising antibacterial agents for future hygiene and medical applications.