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Description
The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA

The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.
ContributorsFauer, Chase Alexander (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS.

One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS. Previous studies have shown that activation of the adenosine receptor signaling pathway through the use of agonists has been demonstrated to increase BBB permeability. For example, regadenoson is an adenosine A2A receptor agonist that has been shown to disrupt the BBB and allow for increased drug uptake in the CNS. The goal of this study was to verify this property of regadenoson. We hypothesized that co-administration of regadenoson with a non-brain penetrant macromolecule would facilitate its entry into the central nervous system. To test this hypothesis, healthy mice were administered regadenoson or saline concomitantly with a fluorescent dextran solution. The brain tissue was either homogenized to measure quantity of fluorescent molecule, or cryosectioned for imaging with confocal fluorescence microscopy. These experiments did not identify any significant difference in the amount of fluorescence detected in the brain after regadenoson treatment. These results contradict those of previous studies and highlight potential differences in injection methodology, time windows, and properties of brain impermeant molecules.
ContributorsWohlleb, Gregory Michael (Author) / Sirianni, Rachael (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still

With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still have some way to go before they are viable systems for drug delivery. One of the main reasons for this is a lack of fabrication processes and systems which produce monodisperse particles while also being feasible for industrialization [10]. This honors thesis investigates various microparticle fabrication techniques \u2014 two using mechanical agitation and one using fluid dynamics \u2014 with the long term goal of incorporating norepinephrine and adenosine into the particles for metabolic stimulatory purposes. It was found that mechanical agitation processes lead to large values for dispersity and the polydispersity index while fluid dynamics methods have the potential to create more uniform and predictable outcomes. The research concludes by needing further investigation into methods and prototype systems involving fluid dynamics methods; however, these systems yield promising results for fabricating monodisperse particles which have the potential to encapsulate a wide variety of therapeutic drugs.
ContributorsRiley, Levi Louis (Author) / Vernon, Brent (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
Morphine is a commonly used analgesic in pain management. Opioid administration to a patient after surgery, such as spinal decompression surgery, can lead to adverse side effects. To demonstrate these adverse side effects could be decreased we created a model of how morphine and its metabolites are transported

Morphine is a commonly used analgesic in pain management. Opioid administration to a patient after surgery, such as spinal decompression surgery, can lead to adverse side effects. To demonstrate these adverse side effects could be decreased we created a model of how morphine and its metabolites are transported and excreted from the body. Using the of morphine and a standard compartment approach this thesis aimed at projecting pharmacokinetics trends of morphine overtime. A Matlab compartment model predicting the transport of morphine through the body can contribute to a better understanding of the concentrations at the systemic level, specifically with respect to a CSF, and what happens when you compare an intravenous injection to a local delivery. Other studies and models commonly utilized patient data over small periods of time2,3,5. An extended period of time will provide information into morphine’s time course after surgery. This model focuses on a compartmentalization of the major organs and the use of a simple Mechalis-Menten enzyme kinetics for the metabolites in the liver. Our results show a CSF concentration of about 1.086×〖10〗^(-12) nmol/L in 6 weeks and 1.0097×〖10〗^(-12) nmol/L in 12 weeks. The concentration profiles in this model are similar to what was expected. The implications of this suggest that patients who reported effects of morphine paste, a locally administered opioid, weeks after the surgery were due to other reasons. In creating a model we can determine important variables and dosage information. This information allows for a greater understanding of what is happening in the body and how to improve surgical outcomes. We propose this study has implications in general research in the pharmacokinetics and dynamics of pharmacology through the body.
ContributorsJacobs, Danielle Renee (Author) / Caplan, Michael (Thesis director) / Giers, Morgan (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Traumatic brain injury (TBI) is a major concern in public health due to its prevalence and effect. Every year, about 1.7 million TBIs are reported [7]. According to the According to the Centers for Disease Control and Prevention (CDC), 5.5% of all emergency department visits, hospitalizations, and deaths from 2002

Traumatic brain injury (TBI) is a major concern in public health due to its prevalence and effect. Every year, about 1.7 million TBIs are reported [7]. According to the According to the Centers for Disease Control and Prevention (CDC), 5.5% of all emergency department visits, hospitalizations, and deaths from 2002 to 2006 are due to TBI [8]. The brain's natural defense, the Blood Brain Barrier (BBB), prevents the entry of most substances into the brain through the blood stream, including medicines administered to treat TBI [11]. TBI may cause the breakdown of the BBB, and may result in increased permeability, providing an opportunity for NPs to enter the brain [3,4]. Dr. Stabenfeldt's lab has previously established that intravenously injected nanoparticles (NP) will accumulate near the injury site after focal brain injury [4]. The current project focuses on confirmation of the accumulation or extravasation of NPs after brain injury using 2-photon microscopy. Specifically, the project used controlled cortical impact injury induced mice models that were intravenously injected with 40nm NPs post-injury. The MATLAB code seeks to analyze the brain images through registration, segmentation, and intensity measurement and evaluate if fluorescent NPs will accumulate in the extravascular tissue of injured mice models. The code was developed with 2D bicubic interpolation, subpixel image registration, drawn dimension segmentation and fixed dimension segmentation, and dynamic image analysis. A statistical difference was found between the extravascular tissue of injured and uninjured mouse models. This statistical difference proves that the NPs do extravasate through the permeable cranial blood vessels in injured cranial tissue.
ContributorsIrwin, Jacob Aleksandr (Author) / Stabenfeldt, Sarah (Thesis director) / Bharadwaj, Vimala (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
With dwindling water resources due to drought and other pressures, water utilities are seeking to tap into alternative water sources as a means to improve water sustainability. Reclaimed water consists of treated wastewater and is widely used for non-potable purposes, such as irrigation, both agricultural and recreational. However, the reclaimed

With dwindling water resources due to drought and other pressures, water utilities are seeking to tap into alternative water sources as a means to improve water sustainability. Reclaimed water consists of treated wastewater and is widely used for non-potable purposes, such as irrigation, both agricultural and recreational. However, the reclaimed water distribution system can be subject to substantial regrowth of microorganisms, including opportunistic pathogens, even following rigorous disinfection. Factors that can influence regrowth include temperature, organic carbon levels, disinfectant type, and the time transported (i.e., water age) in the system. One opportunistic pathogen (OP) that is critical to understanding microbial activity in both reclaimed and drinking water distribution systems is Acanthamoeba. In order to better understand the potential for this amoeba to proliferate in reclaimed water systems and influence other OPs, a simulated reclaimed water distribution system was studied. The objective of this study was to compare the prevalence of Acanthamoeba and one of its endosymbionts, Legionella, across varying assimilable organic carbon (AOC) levels, temperatures, disinfectants, and water ages in a simulated reclaimed water distribution system. The results of the study showed that cooler temperatures, larger water age, and chlorine conditions yielded the lowest detection of Acanthamoeba gene copies per mL or cm2 for bulk water and biofilm samples, respectively.
ContributorsDonaldson, Kandace (Author) / Ankeny, Casey (Thesis director) / Edwards, Marc (Committee member) / Pruden, Amy (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The concentration necessary to kill bacterial biofilms with antimicrobials is the minimum biofilm eradication concentration (MBEC). This is usually determined using an in vitro approach and will vary within different strains of bacteria. Biomedical implants produce biofilm-related infections presenting a unique challenge due to the combination of subpopulations of the

The concentration necessary to kill bacterial biofilms with antimicrobials is the minimum biofilm eradication concentration (MBEC). This is usually determined using an in vitro approach and will vary within different strains of bacteria. Biomedical implants produce biofilm-related infections presenting a unique challenge due to the combination of subpopulations of the bacterial community and the polysaccharide matrix presented by biofilms. The purpose of this investigation is to determine how exposure times in the order of weeks to months affect the MBEC. Using an in vitro approach, Staphylococcus aureus (UAMS-1) and methicillin-resistant Staphylococcus aureus (MRSA) biofilms were produced with a 24 hour growth time and exposed to two antimicrobials, tobramycin and vancomycin, and one combination treatment that consisted of 1:1 tobramycin: vancomycin by weight. Crystal violet screening was used in order to ensure the integrity of the biofilm matrix throughout the full time of exposure. It was determined that UAMS-1 MBECs were lowered after 56 days of exposure than after 5 days for all three treatment groups. MRSA MBECs after 5 days of exposure decreased only with in vancomycin treatment group.
ContributorsSteinhauff, Douglas Busch (Author) / Caplan, Michael (Thesis director) / Overstreet, Derek (Committee member) / Castaneda, Paulo (Committee member) / Materials Science and Engineering Program (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an MR image as well as changes in the temporal dimension and subsequently reconstructs the missing data. This technique has been

Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an MR image as well as changes in the temporal dimension and subsequently reconstructs the missing data. This technique has been shown to retain a high level of fidelity even with an acceleration factor of 5. Currently there exist several different scanner types that each have their separate analytical methods in MATLAB. A graphical user interface (GUI) was created to facilitate a single computing platform for these different scanner types in order to improve the ease and efficiency with which researchers and clinicians interact with this technique. A GUI was successfully created for both prospective and retrospective MRSI data analysis. This GUI retained the original high fidelity of the reconstruction technique and gave the user the ability to load data, load reference images, display intensity maps, display spectra mosaics, generate a mask, display the mask, display kspace and save the corresponding spectra, reconstruction, and mask files. Parallelization of the reconstruction algorithm was explored but implementation was ultimately unsuccessful. Future work could consist of integrating this parallelization method, adding intensity overlay functionality and improving aesthetics.
ContributorsLammers, Luke Michael (Author) / Kodibagkar, Vikram (Thesis director) / Hu, Harry (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description

Traumatic brain injury (TBI), a neurological condition that negatively affects neural capabilities, occurs when a blunt trauma impacts the head. Following the initial injury that immediately impacts neural cell function and survival, a series of secondary injury events lead to substantial sustained inflammation for weeks to years post-injury. To develo

Traumatic brain injury (TBI), a neurological condition that negatively affects neural capabilities, occurs when a blunt trauma impacts the head. Following the initial injury that immediately impacts neural cell function and survival, a series of secondary injury events lead to substantial sustained inflammation for weeks to years post-injury. To develop TBI treatments that may stimulate regenerative processes, a novel drug delivery system that efficiently delivers the appropriate drug/payload to injured tissue is crucial. Hyaluronic acid (HA) hydrogels are attractive when developing a biomaterial for tissue reparation and regeneration. HA is a natural polymer with physicochemical properties that can be tuned to match the properties of the extracellular matrix (ECM) of the many tissues including the central nervous system (CNS). Here, the project objective was to develop a HA hydrogel system for local delivery of a biological payload; this objective was completed by employing a composite system with two parts. The first part is an injectable, shear-thinning bulk hydrogel, and the second is microgels for loading biological payloads. The bulk hydrogel was composed of cyclodextrin modified HA (Cd-HA) and adamantane modified HA (Ad-HA) that give rise to guest-host interactions that facilitate physical crosslinking. The microgel, composed of norbornene-HA (Nor-HA) and sulfated-HA, crosslink via chemical crosslinks upon activation of a UV photoinitiator. The sulfated-HA microgels facilitate loading of biological payloads by mimicking heparin binding sites via the conjugated sulfated group. Neuregulin I, an epidermal growth factor with neuroprotective properties, is one such protein with a heparin binding domain that may be retained in the sulfated-HA microgels. Specifically, the project focused on mechanical testing of this composite microgel/hydrogel system and also developing protein affinity assays.

ContributorsKylat, Anna (Author) / Stabenfeldt, Sarah (Thesis director) / Holloway, Julianne (Committee member) / Jensen, Gregory (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
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Description
The aim of the present study was to review the symptoms and current treatment options of the most common skin infections seen in outpatient settings and develop a preliminary alternative treatment solution. The specific skin infections evaluated were those caused by Staphylococcus and Streptococcus bacterial species, and are frequently treated

The aim of the present study was to review the symptoms and current treatment options of the most common skin infections seen in outpatient settings and develop a preliminary alternative treatment solution. The specific skin infections evaluated were those caused by Staphylococcus and Streptococcus bacterial species, and are frequently treated with a wide variety of systemic antibiotics or topical ointments. Systemic antibiotics have shown increased occurrence of adverse side effects as well as the development of antibiotic-resistant bacteria. Additionally, these medications are usually overprescribed, which may further exacerbate negative side effects. Another issue that is addressed is the development of infections following treatment of a new laceration or other trauma to the skin. A patient may be treated for their wound with stitches or another alternative, but there is still the possibility of developing an infection later.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.
ContributorsTanner, Emily Christine (Author) / Pizziconi, Vincent (Thesis director) / Nguyen, Eric (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05