Matching Items (22)
Filtering by
- All Subjects: Biomaterials
- All Subjects: Drug Delivery
- Creators: Harrington Bioengineering Program
- Member of: Theses and Dissertations
Description
The goal of this research project is to create a Mathcad template file capable of statistically modelling the effects of mean and standard deviation on a microparticle batch characterized by the log normal distribution model. Such a file can be applied during manufacturing to explore tolerances and increase cost and time effectiveness. Theoretical data for the time to 60% drug release and the slope and intercept of the log-log plot were collected and subjected to statistical analysis in JMP. Since the scope of this project focuses on microparticle surface degradation drug release with no drug diffusion, the characteristic variables relating to the slope (n = diffusional release exponent) and the intercept (k = kinetic constant) do not directly apply to the distribution model within the scope of the research. However, these variables are useful for analysis when the Mathcad template is applied to other types of drug release models.
ContributorsHan, Priscilla (Author) / Vernon, Brent (Thesis director) / Nickle, Jacob (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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 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
Description
Cardiac tissue engineering is an emerging field that has the potential to regenerate and repair damaged cardiac tissues after myocardial infarction. Numerous studies have introduced hydrogel-based cardiac tissue constructs featuring suitable microenvironments for cell growth along with precise surface topographies for directed cell organization. Despite significant progress, previously developed cardiac tissue constructs have suffered from electrically insulated matrices and low cell retention. To address these drawbacks, we fabricated micropatterned hybrid hydrogel constructs (uniaxial microgrooves with 50 µm with) using a photocrosslinkable gelatin methacrylate (GelMA) hydrogel incorporated with gold nanorods (GNRs). The electrical impedance results revealed a lower impedance in the GelMA-GNR constructs versus the pure GelMA constructs. Superior electrical conductivity of GelMA-GNR hydrogels (due to incorporation of GNRs) enabled the hybrid tissue constructs to be externally stimulated using a pulse generator. Furthermore, GelMA-GNR tissue hydrogels were tested to investigate the biological characteristics of cultured cardiomyocytes. The F-actin fiber analysis results (area coverage and alignment indices) revealed higher directed (uniaxial) cytoskeleton organization of cardiac cells cultured on the GelMA-GNR hydrogel constructs in comparison to pure GelMA. Considerable increase in the coverage area of cardiac-specific markers (sarcomeric α-actinin and connexin 43) were observed on the GelMA-GNR hybrid constructs compared to pure GelMA hydrogels. Despite substantial dissimilarities in cell organization, both pure GelMA and hybrid GelMA-GNR hydrogel constructs provided a suitable microenvironment for synchronous beating of cardiomyocytes.
ContributorsMoore, Nathan Allen (Author) / Nikkhah, Mehdi (Thesis director) / Smith, Barbara (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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. 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
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 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.
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
Description
There is an increasing interest in developing thermo-responsive polymers for treating aneurysms. In this thesis project, the potential for poly(NIPAAm-co-JAAm-co-HEMA-Acrylate) (PNJHAc) as a treatment method for brain aneurysms was investigated. Five different batches of polymer were synthesized, purified, lyophilized, and characterized using nuclear magnetic resonance and cloud point techniques over the course of several months. Two were tested in aneurysm models. Of these five batches, there were two that showed promise as liquid embolic agents for endovascular embolization.
ContributorsLoui, Michelle (Author) / Vernon, Brent (Thesis director) / Pal, Amrita (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Previous studies have found that the detection of near-threshold stimuli is decreased immediately before movement and throughout movement production. This has been suggested to occur through the use of the internal forward model processing an efferent copy of the motor command and creating a prediction that is used to cancel out the resulting sensory feedback. Currently, there are no published accounts of the perception of tactile signals for motor tasks and contexts related to the lips during both speech planning and production. In this study, we measured the responsiveness of the somatosensory system during speech planning using light electrical stimulation below the lower lip by comparing perception during mixed speaking and silent reading conditions. Participants were asked to judge whether a constant near-threshold electrical stimulation (subject-specific intensity, 85% detected at rest) was present during different time points relative to an initial visual cue. In the speaking condition, participants overtly produced target words shown on a computer monitor. In the reading condition, participants read the same target words silently to themselves without any movement or sound. We found that detection of the stimulus was attenuated during speaking conditions while remaining at a constant level close to the perceptual threshold throughout the silent reading condition. Perceptual modulation was most intense during speech production and showed some attenuation just prior to speech production during the planning period of speech. This demonstrates that there is a significant decrease in the responsiveness of the somatosensory system during speech production as well as milliseconds before speech is even produced which has implications for speech disorders such as stuttering and schizophrenia with pronounced deficits in the somatosensory system.
ContributorsMcguffin, Brianna Jean (Author) / Daliri, Ayoub (Thesis director) / Liss, Julie (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Advancements in healthcare and the emergence of an aging population has led to an increase in the number of prosthetic joint procedures in the United States. According to Healthcare Cost and Utilization Project, 660,876 and 348,970 total hip and knee arthroplasties were performed in 2014[1].The percentage of total hip or knee procedures that are revised due to an infection is 1.23% and 1.21% respectively[3], [4]. Although the percent of infections may be small, an infection can have a tremendous burden on the patient and healthcare system. It is expected that prosthetic joint infections (PJIs) will cost the healthcare system an estimated $1.62 billion by 2020[5]. PJIs are often difficult to treat due to the formation of biofilm at the site of the infection. A large majority of PJIs are the result of a bacterial biofilm, but around 1% of PJIs are due to fungal infections[3]. The current method of treatment is to surgically remove all infected tissue at the site of infection through a process called debridement and then insert a medicated bone cement spacer[7], [10]–[12]. One such medication that is loaded into the bone cement is caspofungin, a member of the echinocandin class of compounds that inhibit the synthesis of 1,3-β-D-glucan which is a crucial element of the cell wall of the target fungi[13]–[15]. For the studies reported herein, the caspofungin-loaded bone cement samples were made at 5 dosage strengths according to standard operating room practices. The elution of the drug was analyzed using ultraviolet spectrophotometry. The elution profiles were analyzed for 19 days consecutively, during which the 70 mg, 1 g, and 5 g dosage groups showed a prolonged, sustained release of the caspofungin. The 70 mg and 1 g dosage cumulative mass release profiles were not statistically significant, but it is unlikely that the difference would not have a clinical significance especially in the treatment of a fungal biofilm infection. The determination of the elution profile for caspofungin from loaded-bone cement can provide clinicians with a basis for how the drug will release into the infected joint.
ContributorsMoore, Rex C. (Author) / Vernon, Brent (Thesis director) / Overstreet, Derek (Committee member) / Industrial, Systems & Operations Engineering Prgm (Contributor) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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 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
Description
With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.
ContributorsUwiringiyimana, Mahoro Marie Chantal (Author) / Vernon, Brent (Thesis director) / Nikkhah, Mehdi (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05