Matching Items (7)
Filtering by

Clear all filters

151067-Thumbnail Image.png

Temperature-responsive hydrogels with controlled water content and their development toward drug delivery and embolization applications

Description
Aqueous solutions of temperature-responsive copolymers based on N-isopropylacrylamide (NIPAAm) hold promise for medical applications because they can be delivered as liquids and quickly form gels in the body without organic solvents or chemical reaction. However, their gelation is often followed by phase-separation and shrinking. Gel shrinking and water loss is…

Aqueous solutions of temperature-responsive copolymers based on N-isopropylacrylamide (NIPAAm) hold promise for medical applications because they can be delivered as liquids and quickly form gels in the body without organic solvents or chemical reaction. However, their gelation is often followed by phase-separation and shrinking. Gel shrinking and water loss is a major limitation to using NIPAAm-based gels for nearly any biomedical application. In this work, a graft copolymer design was used to synthesize polymers which combine the convenient injectability of poly(NIPAAm) with gel water content controlled by hydrophilic side-chain grafts based on Jeffamine® M-1000 acrylamide (JAAm). The first segment of this work describes the synthesis and characterization of poly(NIPAAm-co-JAAm) copolymers which demonstrates controlled swelling that is nearly independent of LCST. The graft copolymer design was then used to produce a degradable antimicrobial-eluting gel for prevention of prosthetic joint infection. The resorbable graft copolymer gels were shown to have three unique characteristics which demonstrate their suitability for this application. First, antimicrobial release is sustained and complete within 1 week. Second, the gels behave like viscoelastic fluids, enabling complete surface coverage of an implant without disrupting fixation or movement. Finally, the gels degrade rapidly within 1-6 weeks, which may enable their use in interfaces where bone healing takes place. Graft copolymer hydrogels were also developed which undergo Michael addition in situ with poly(ethylene glycol) diacrylate to form elastic gels for endovascular embolization of saccular aneurysms. Inclusion of JAAm grafts led to weaker physical crosslinking and faster, more complete chemical crosslinking. JAAm grafts prolonged the delivery window of the system from 30 seconds to 220 seconds, provided improved gel swelling, and resulted in stronger, more elastic gels within 30 minutes after delivery.
ContributorsOverstreet, Derek (Author) / Caplan, Michael (Thesis advisor) / Massia, Stephen (Committee member) / Mclaren, Alexander (Committee member) / Vernon, Brent (Committee member) / McLemore, Ryan (Committee member) / Arizona State University (Publisher)
Created2012
133170-Thumbnail Image.png

Norepinephrine and Adenosine Infused Microparticles for Brown Adipose Tissue Stimulation

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
148276-Thumbnail Image.png

In Vitro Release Study of L-Tyrosine-Loaded PLGA Microparticles

Description

Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo…

Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo from the bodily environment, and reduction in systemic side effects. This experiment used a single emulsion technique to encapsulate L-tyrosine in PLGA microparticles and UV spectrophotometry to analyze the drug release over a period of one week. The release assay found that for the tested samples, the released amount is distinct initially, but is about the same after 4 days, and they generally follow the same normalized percent released pattern. The experiment could continue with testing more samples, test the same samples for a longer duration, and look into higher w/w concentrations such as 20% or 50%.
ContributorsSeo, Jinpyo (Author) / Vernon, Brent (Thesis director) / Pal, Amrita (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05

Statistical Modeling of Drug Release from Spherical Surface-Degrading Particle Batch

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…

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

Examining the Mechanisms of a Functionalized Collagen-PRP Hydrogel for Chronic Wound Healing Applications

Description

Chronic wounds affect many people worldwide and significantly impact their quality of life. Hydrogel wound dressings are a promising option for chronic wounds due to their properties, including mild fabrication conditions, high water content, biodegradability, and bioactive molecule delivery capabilities. This thesis will explore the mechanisms that contribute to the…

Chronic wounds affect many people worldwide and significantly impact their quality of life. Hydrogel wound dressings are a promising option for chronic wounds due to their properties, including mild fabrication conditions, high water content, biodegradability, and bioactive molecule delivery capabilities. This thesis will explore the mechanisms that contribute to the wound healing properties of a bovine type I collagen-based hydrogel that incorporates platelet-rich plasma and describe how this hydrogel will be capable of effectively healing chronic wounds.
ContributorsHatch, Trevor (Author) / Stabenfeldt, Sarah (Thesis director) / Vernon, Brent (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
171760-Thumbnail Image.png

Utilizing Injection Molding to Generate Complex Three-Dimensional Cell Encapsulation Geometries

Description
Encapsulation is a promising technology to deliver cell-based therapies to patients safely and with reduced need for immunosuppression. Macroencapsulation devices are advantageous due to their ease of retrieval, and thus enhanced safety profile, relative to microencapsulation techniques. A major challenge in macroencapsulation device design is ensuring sufficient oxygen transport to…

Encapsulation is a promising technology to deliver cell-based therapies to patients safely and with reduced need for immunosuppression. Macroencapsulation devices are advantageous due to their ease of retrieval, and thus enhanced safety profile, relative to microencapsulation techniques. A major challenge in macroencapsulation device design is ensuring sufficient oxygen transport to encapsulated cells, requiring high surface area-to-volume device geometries. In this work, a hydrogel injection molding biofabrication method was modified to design and generate complex three-dimensional macroencapsulation devices that have greater complexity in the z-axis. The rheological properties of diverse hydrogels were evaluated and used to perform computational flow modeling within injection mold devices to evaluate pressure regimes suitable for cell viability. 3D printed device designs were evaluated for the reproducibility of hydrogel filling and extraction. This work demonstrated that injection molding biofabrication to construct complex three-dimensional geometries is feasible in pressure regimes consistent with preserving cell viability. Future work will evaluate encapsulated cell viability after injection molding.
ContributorsBrowning, Blake (Author) / Weaver, Jessica D (Thesis advisor) / Vernon, Brent (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2022
131712-Thumbnail Image.png

NIPAAm co-DEAEMA Hydrogels Prolong Ketorolac Release

Description
NIPAAm co-DEAEMA hydrogels are a potential solution for sustained, local delivery of ketorolac tromethamine. Current methods of postoperative pain management, such as local anesthetics, NSAIDs, and opioids, can be improved by minimizing side effects while still effectively treating severe and extreme pain. Though high doses of ketorolac can be toxic,…

NIPAAm co-DEAEMA hydrogels are a potential solution for sustained, local delivery of ketorolac tromethamine. Current methods of postoperative pain management, such as local anesthetics, NSAIDs, and opioids, can be improved by minimizing side effects while still effectively treating severe and extreme pain. Though high doses of ketorolac can be toxic, sustained, local delivery via hydrogels offers a promising solution. Four ketorolac release studies were conducted using PNDJ hydrogels formulated by Sonoran Biosciences. The first two studies tested a range of JAAm concentration between 1.4 and 2.2 mole percent. Both had high initial release rates lasting less than 7 days and appeared to be unaffected by JAAm content. Tobramycin slowed down the release of ketorolac but was unable to sustain release for more than 6 days. Incorporating DEAEMA prolonged the release of ketorolac for up to 14 days with significant reductions in initial burst release rate. Low LCST of NIPAAM co-DEAEMA polymer is problematic for even drug distribution and future in vivo applications.
ContributorsHui, Nathan (Author) / Vernon, Brent (Thesis director) / Heffernan, John (Committee member) / School of International Letters and Cultures (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05