Chemicals and Drugs Commons^™

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Coordinated Unmanned Aircraft System (Uas) And Ground-Based Weather Measurements To Predict Lagrangian Coherent Structures (Lcss), Peter J. Nolan, James Pinto, Javier González-Rocha, Anders Jensen, Christina N. Vezzi, Sean C. C. Bailey, Gijs De Boer, Constantin Diehl, Roger Laurence Iii, Craig W. Powers, Hosein Foroutan, Shane D. Ross, David G. Schmale Iii

Mechanical Engineering Faculty Publications

Concentrations of airborne chemical and biological agents from a hazardous release are not spread uniformly. Instead, there are regions of higher concentration, in part due to local atmospheric flow conditions which can attract agents. We equipped a ground station and two rotary-wing unmanned aircraft systems (UASs) with ultrasonic anemometers. Flights reported here were conducted 10 to 15 m above ground level (AGL) at the Leach Airfield in the San Luis Valley, Colorado as part of the Lower Atmospheric Process Studies at Elevation—a Remotely-Piloted Aircraft Team Experiment (LAPSE-RATE) campaign in 2018. The ultrasonic anemometers were used to collect simultaneous measurements of …

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

The Role Of Catalytic Residue PKA On The Hydrolysis/Transglycosylation Partition In Family 3 Β-Glucosidases, Inacrist Geronimo, Christina M. Payne, Mats Sandgren

Chemical and Materials Engineering Faculty Publications

β-Glucosidases (βgls) primarily catalyze the hydrolysis of the terminal glycosidic bond at the non-reducing end of β-glucosides, although glycosidic bond synthesis (called transglycosylation) can also occur in the presence of another acceptor. In the final reaction step, the glucose product or another substrate competes with water for transfer to the glycosyl-enzyme intermediate. The factors governing the balance between the two pathways are not fully known; however, the involvement of ionizable residues in binding and catalysis suggests that their pK_a may play a role. Through constant pH molecular dynamics simulations of a glycoside hydrolase Family 3 (GH3) βgl, we …

Improving The Thermal Stability Of Cellobiohydrolase Cel7a From Hypocrea Jecorina By Directed Evolution, Frits Goedegebuur, Lydia Dankmeyer, Peter Gualfetti, Saeid Karkehabadi, Henrik Hansson, Suvamay Jana, Vicky Huynh, Bradley R. Kelemen, Paulien Kruithof, Edmund A. Larenas, Pauline J. M. Teunissen, Jerry Ståhlberg, Christina M. Payne, Colin Mitchinson, Mats Sandgren

Chemical and Materials Engineering Faculty Publications

Secreted mixtures of Hypocrea jecorina cellulases are able to efficiently degrade cellulosic biomass to fermentable sugars at large, commercially relevant scales. H. jecorina Cel7A, cellobiohydrolase I, from glycoside hydrolase family 7, is the workhorse enzyme of the process. However, the thermal stability of Cel7A limits its use to processes where temperatures are no higher than 50 °C. Enhanced thermal stability is desirable to enable the use of higher processing temperatures and to improve the economic feasibility of industrial biomass conversion. Here, we enhanced the thermal stability of Cel7A through directed evolution. Sites with increased thermal stability properties were combined, and …

Recent Advances On Iron Oxide Magnetic Nanoparticles As Sorbents Of Organic Pollutants In Water And Wastewater Treatment, Angela M. Gutierrez, Thomas D. Dziubla, J. Zach Hilt

Superfund Research Center Faculty Publications

The constant growth in population worldwide over the past decades continues to put forward the need to provide access to safe, clean water to meet human needs. There is a need for cost-effective technologies for water and wastewater treatment that can meet the global demands and the rigorous water quality standards and at the same maximizing pollutant efficiency removal. Current remediation technologies have failed in keeping up with these factors without becoming cost-prohibitive. Most recently, nanotechnology has been sought as the best alternative to increase access to water supplies by remediating those already contaminated and offering ways to access unconventional …

Inhibition Of Mammalian Glycoprotein Ykl-40 Identification Of The Physiological Ligand, Abhishek A. Kognole, Christina M. Payne

Chemical and Materials Engineering Faculty Publications

YKL-40 is a mammalian glycoprotein associated with progression, severity, and prognosis of chronic inflammatory diseases and a multitude of cancers. Despite this well documented association, identification of the lectin′s physiological ligand and, accordingly, biological function has proven experimentally difficult. YKL-40 has been shown to bind chito-oligosaccharides; however, the production of chitin by the human body has not yet been documented. Possible alternative ligands include proteoglycans, polysaccharides, and fibers like collagen, all of which makeup the extracellular matrix. It is likely that YKL-40 is interacting with these alternative polysaccharides or proteins within the body, extending its function to cell biological roles …

Toward Biochemical Conversion Of Lignocellulose On-Farm: Pretreatment And Hydrolysis Of Corn Stover In Situ, Alicia A. Modenbach, Sue E. Nokes, Michael D. Montross, Barbara L. Knutson

Biosystems and Agricultural Engineering Faculty Publications

High-solids lignocellulosic pretreatment using NaOH followed by high-solids enzymatic hydrolysis was evaluated for an on-farm biochemical conversion process. Increasing the solids loadings for these processes has the potential for increasing glucose concentrations and downstream ethanol production; however, sequential processing at high-solids loading similar to an on-farm cellulose conversion system has not been studied. This research quantified the effects of high-solids pretreatment with NaOH and subsequent high-solids enzymatic hydrolysis on cellulose conversion. As expected, conversion efficiency was reduced; however, the highest glucose concentration (40.2 g L^-1), and therefore the highest potential ethanol concentration, resulted from the high-solids combined pretreatment …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Lipid Extraction From Scenedesmus Sp. Microalgae For Biodiesel Production Using Hot Compressed Hexane, Hee-Yong Shin, Jae-Hun Ryu, Seong-Youl Bae, Czarena L. Crofcheck, Mark Crocker

Center for Applied Energy Research Faculty and Staff Publications

Lipid extraction from Scenedesmus sp. microalgae using hot compressed hexane (HCH) was investigated. Extraction performance was evaluated near the critical point of hexane and was compared with that of hexane extraction performed at room temperature and pressure, and the Bligh and Dyer extraction method. Experimental data showed that HCH significantly improves the lipid yield and rate of lipid extraction compared to the use of hexane at ambient conditions. High yields of biodiesel-convertible lipid fractions were rapidly achieved at the critical point of hexane, at a level comparable to that of the Bligh and Dyer method.

Effects Of Sodium Hydroxide Pretreatment On Structural Components Of Biomass, Alicia A. Modenbach, Sue E. Nokes

Biosystems and Agricultural Engineering Faculty Publications

Pretreatment is a unit operation in the conversion of biomass to valuable products that utilizes various combinations of conditions, including chemicals, heat, pressure, and time, to reduce the recalcitrance of lignocellulose. Many such pretreatments have been developed over the years, as the operating conditions can be adapted so that lignocellulose is modified in ways unique to each pretreatment. By tailoring pretreatment conditions to achieve these modifications, the types of final products produced can be controlled. The purpose of this review is to provide a consolidated source of information for sodium hydroxide effects on lignocellulose. The structural characteristics of lignocellulose and …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Bioerodible Calcium Sulfate Bone Grafting Substitutes With Tailored Drug Delivery Capabilities, Bryan R. Orellana

Theses and Dissertations--Biomedical Engineering

Bone regeneration or augmentation is often required prior to or concomitant with implant placement. With the limitations of many existing technologies, a biologically compatible synthetic bone grafting substitute that is osteogenic, bioerodible, and provides spacing-making functionality while acting as a drug delivery vehicle for bioactive molecules could provide an alternative to ‘gold standard’ techniques.

In the first part of this work, calcium sulfate (CS) space-making synthetic bone grafts with uniformly embedded poly(β-amino ester) (PBAE) biodegradable hydrogel particles was developed to allow controlled release of bioactive agents. The embedded gel particles’ influence on the physical and chemical characteristics of CS was …

Enzymatic Hydrolysis Of Biomass At High-Solids Loadings – A Review, Alicia A. Modenbach, Sue E. Nokes

Biosystems and Agricultural Engineering Faculty Publications

Enzymatic hydrolysis is the unit operation in the lignocellulose conversion process that utilizes enzymes to depolymerize lignocellulosic biomass. The saccharide components released are the feedstock for fermentation. When performed at high-solids loadings (≥ 15% solids, w/w), enzymatic hydrolysis potentially offers many advantages over conversions performed at low- or moderate-solids loadings, including increased sugar and ethanol concentrations and decreased capital and operating costs.

The goal of this review is to provide a consolidated source of information on studies using high-solids loadings in enzymatic hydrolysis. Included in this review is a brief discussion of the limitations, such as a lack of available …

Optimization Of Solid-State Fermentation Parameters For The Production Of Xylanase By Trichoderma Longibrachiatum On Wheat Bran In A Forced Aeration System, Elizabeth R. Ridder, Sue E. Nokes, Barbara L. Knutson

Biosystems and Agricultural Engineering Faculty Publications

The effect of aeration on the production of xylanase by Trichoderma longibrachiatum on wheat bran in a solid-state fermentation (SSF) system has not been investigated. This study was conducted to investigate the interactive effects of aeration, initial moisture content of the substrate, and depth of the substrate on xylanase activity produced in a tray fermenter. The experiment was conducted as a split plot experiment with factorial treatments and three replications of each treatment combination. The whole plot treatment was aeration rate (0, 2.9, 5.7 L/min/kg bran). Initial moisture content (45, 55, 65% w.b.) and depth of substrate (1.0 and 2.5 …

Optimization Of Solid-State Fermentation Parameters For The Production Of Xylanase By Trichoderma Longibrachiatum On Wheat Bran, Elizabeth R. Ridder, Sue E. Nokes, Barbara L. Knutson

Biosystems and Agricultural Engineering Faculty Publications

Solid-state fermentation has the potential to produce inexpensive enzymes for use in high-volume industrial applications. Process parameters such as substrate moisture content and length of fermentation can have a significant effect on the amount and timing of enzyme production. This study was conducted in two stages, a screening stage and an optimization stage, to determine the effects of moisture content of the substrate, surfactant addition upon inoculation, depth of the substrate, and duration of fermentation on xylanase activity produced by Trichoderma longibrachiatum. Screening fermentations were conducted at 25°C, 50 and 75% wet basis moisture content (w.b.), 0.0 and 0.2% …