Mesoporous silica- and silicon-based materials as carriers for poorly water soluble drugs

New chemical entities with unfavorable water solubility properties are continuously emerging in drug discovery. Without pharmaceutical manipulations inefficient concentrations of these drugs in the systemic circulation are probable. Typically, in order to be absorbed from the gastrointestinal tract, the drug has to be dissolved. Several methods have been developed to improve the dissolution of poorly soluble drugs. In this study, the applicability of different types of mesoporous (pore diameters between 2 and 50 nm) silicon- and silica-based materials as pharmaceutical carriers for poorly water soluble drugs was evaluated. Thermally oxidized and carbonized mesoporous silicon materials, ordered mesoporous silicas MCM-41 and SBA-15, and non-treated mesoporous silicon and silica gel were assessed in the experiments. The characteristic properties of these materials are the narrow pore diameters and the large surface areas up to over 900 m²/g. Loading of poorly water soluble drugs into these pores restricts their crystallization, and thus, improves drug dissolution from the materials as compared to the bulk drug molecules. In addition, the wide surface area provides possibilities for interactions between the loaded substance and the carrier particle, allowing the stabilization of the system. Ibuprofen, indomethacin and furosemide were selected as poorly soluble model drugs in this study. Their solubilities are strongly pH-dependent and the poorest (< 100 µg/ml) at low pH values. The pharmaceutical performance of the studied materials was evaluated by several methods. In this work, drug loading was performed successfully using rotavapor and fluid bed equipment in a larger scale and in a more efficient manner than with the commonly used immersion methods. It was shown that several carrier particle properties, in particular the pore diameter, affect the loading efficiency (typically ~25-40 w-%) and the release rate of the drug from the mesoporous carriers. A wide pore diameter provided easier loading and faster release of the drug. The ordering and length of the pores also affected the efficiency of the drug diffusion. However, these properties can also compensate the effects of each other. The surface treatment of porous silicon was important in stabilizing the system, as the non-treated mesoporous silicon was easily oxidized at room temperature. Different surface chemical treatments changed the hydrophilicity of the porous silicon materials and also the potential interactions between the loaded drug and the particle, which further affected the drug release properties. In all of the studies, it was demonstrated that loading into mesoporous silicon and silica materials improved the dissolution of the poorly soluble drugs as compared to the corresponding bulk compounds (e.g. after 30 min ~2-7 times more drug was dissolved depending on the materials). The release profile of the loaded substances remained similar also after 3 months of storage at 30°C/56% RH. The thermally carbonized mesoporous silicon did not compromise the Caco-2 monolayer integrity in the permeation studies and improved drug permeability was observed. The loaded mesoporous silica materials were also successfully compressed into tablets without compromising their characteristic structural and drug releasing properties. The results of this research indicated that mesoporous silicon/silica-based materials are promising materials to improve the dissolution of poorly water soluble drugs. Their feasibility in pharmaceutical laboratory scale processes was also confirmed in this thesis.

Excision of uracil from the ends of double stranded DNA by uracil DNA glycosylase and its use in high efficiency cloning of PCR products

We show that uracil DNA glycosylase from E. coli excises uracil residues from the ends of double stranded oligos. This information has allowed us to develop an efficient method of cloning PCR amplified DNA. In this report, we describe use of this method in cloning of E. coli genes for lysyl- and methionyl-tRNA synthetases. Efficiency of cloning by this method was found to be the same as that of subcloning of DNA restriction fragments from one vector to the other vector. Possibilities of using other DNA glycosylases for such applications are discussed.

Optimal crop planning and conjunctive use of water resources in a coastal river basin

Due to increasing trend of intensive rice cultivation in a coastal river basin, crop planning and groundwater management are imperative for the sustainable agriculture. For effective management, two models have been developed viz. groundwater balance model and optimum cropping and groundwater management model to determine optimum cropping pattern and groundwater allocation from private and government tubewells according to different soil types (saline and non-saline), type of agriculture (rainfed and irrigated) and seasons (monsoon and winter). A groundwater balance model has been developed considering mass balance approach. The components of the groundwater balance considered are recharge from rainfall, irrigated rice and non-rice fields, base flow from rivers and seepage flow from surface drains. In the second phase, a linear programming optimization model is developed for optimal cropping and groundwater management for maximizing the economic returns. The models developed were applied to a portion of coastal river basin in Orissa State, India and optimal cropping pattern for various scenarios of river flow and groundwater availability was obtained.

Exploring use of climate information for optimal design of water resources infrastructure

We conducted surveys of fire and fuels managers at local, regional, and national levels to gain insights into decision processes and information flows in wildfire management. Survey results in the form of fire managers’ decision calendars show how climate information needs vary seasonally, over space, and through the organizational network, and help determine optimal points for introducing climate information and forecasts into decision processes. We identified opportunities to use climate information in fire management, including seasonal to interannual climate forecasts at all organizational levels, to improve the targeting of fuels treatments and prescribed burns, the positioning and movement of initial attack resources, and staffing and budgeting decisions. Longer-term (5–10 years) outlooks also could be useful at the national level in setting budget and research priorities. We discuss these opportunities and examine the kinds of organizational changes that could facilitate effective use of existing climate information and climate forecast capabilities.

Improvements to Data Collection in Commercial Fisheries Using Electronic Reporting Methods: Cost/Efficiency and Implications for Use in Ecosystem Management.

Data have been collected on fisheries catch and effort trends since the latter half of the 1800s. With current trends in declining stocks and stricter management regimes, data need to be collected and analyzed over shorter periods and at finer spatial resolution than in the past. New methods of electronic reporting may reduce the lag time in data collection and provide more accurate spatial resolution. In this study I evaluated the differences between fish dealer and vessel reporting systems for federal fisheries in the US New England and Mid-Atlantic areas. Using data on landing date, report date, gear used, port landed, number of hauls, number of fish sampled and species quotas from available catch and effort records I compared dealer and vessel electronically collected data against paper collected dealer and vessel data to determine if electronically collected data are timelier and more accurate. To determine if vessel or dealer electronic reporting is more useful for management, I determined differences in timeliness and accuracy between vessel and dealer electronic reports. I also compared the cost and efficiency of these new methods with less technology intensive reporting methods using available cost data and surveys of seafood dealers for cost information. Using this information I identified potentially unnecessary duplication of effort and identified applications in ecosystem-based fisheries management. This information can be used to guide the decisions of fisheries managers in the United States and other countries that are attempting to identify appropriate fisheries reporting methods for the management regimes under consideration. (PDF contains 370 pages)

Studies on the nutrition of brackish water catfish - Chrysichthys nigrodigitatus . 1. Preliminary investigations on the probable use of vegetable oil in catfish feeds

Four groups of brackishwater catfish were fed four diets: N.F. (NIOMR formula 1 feed), A. B. and C. for seven weeks. Feeds N.F., A., B and C. contained 1.21% fish oil + 5.59% vegetable oil; 1.21% fish oil + 7.39% vegetable oil; 1.21% fish oil + 9.09% vegetable oil; 1.21% fish oil + 10.89% vegetable oil respectively. Results of feeding trial showed that growth was best in the group fed diets containing 10.89% vegetable oil and least in those containing 9.09% vegetable oil

Effects of land use and physicochemical water quality on grass shrimp, Palaemonetes pugio, and its parasitic isopod, Probopyrus pandalicola, in South Carolina, USA tidal creeks

Grass shrimp, Palaemonetes pugio, are a common inhabitant of US East and Gulf coast salt marshes and are a food source for recreationally and economically important fish and crustacean species. Due to the relationship of grass shrimp with their ecosystem, any significant changes in grass shrimp population may have the potential to affect the estuarine system. Land use is a crucial concern in coastal areas where increasing development impacts the surrounding estuaries and salt marshes and has made grass shrimp population studies a logical choice to investigate urbanization effects. Any impact on tidal creeks will be an impact on grass shrimp populations and their associated micro-environment whether predator, prey or parasitic symbiont. Anthropogenic stressors introduced into the grass shrimp ecosystem may even change the intensity of infections from parasitic symbionts. An ectoparasite found on P. pugio is the bopyrid isopod Probopyrus pandalicola. Little is known about factors that may affect the occurrence of this isopod in grass shrimp populations. The goal was to analyze the prevalence of P. pandalicola in grass shrimp in relation to land use classifications, water quality parameters, and grass shrimp population metrics. Eight tidal creeks in coastal South Carolina were sampled monthly over a three year period. The occurrence of P. pandalicola ranged from 1.2% to 5.7%. Analysis indicated that greater percent water and marsh coverage resulted in a higher incidence of bopyrid occurrence. Analysis also indicated that higher bopyrid incidence occurred in creeks with higher salinity, temperature, and pH but lower dissolved oxygen. The land use characteristics found to limit bopyrid incidence were limiting to grass shrimp (definitive host) populations and probably copepod (intermediate host) populations as well.

A note on the use of ground water for successful breeding of common carps in extremely cold climate

Common carps are known for prolific breeding habits but they generally do not breed in water with temperature value less than 20 degree C. During winter months of 1985 when the temperature ranged from 15.5-20.5 degree C, the common carps were successfully bred by using ground water having temperature of 25-26 degree C and the results are discussed.

Preliminary observations of the use of under-water light in fish catch

Experiments with drift gill net with under-water lights were carried out in the sea and estuarine region along with a control net of the same specifications without any light in the same fishing ground for comparison. The experimental net caught more fish in number and weight than the control. Fishes like pomfrets (Pampus chinensis, Parastromafeus niger), seer (Scomberomorus spp), hilsa (Ilisha spp) etc showed positive phototaxis and were gilled encircling the point of illumination. Young skates (Mobula spp) and Polynemus tetradactylus were antiphototactic. The number of fishes caught increased with increase in period of illumination. The catch of larger fishes was maximum at 60 mts of illumination and the total catch increased with increase in intensity of light. Additional cost of operation with under-water light was Rs 1-25 per hr but the catch was 4 to 5 times greater than that of the control net.