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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
Description
This report provides information concerning qualities of methylcellulose and how those properties affect further experimentation within the biomedical world. Utilizing the compound’s biocompatibility many issues, ranging from surgical to cosmetic, can be solved. As of recent, studies indicate, methylcellulose has been used as a physically cross-linked gel, which cannot sustain a solid form within the body. Therefore, this report will ultimately explore the means of creating a non-degradable, injectable, chemically cross-linking methylcellulose- based hydrogel. Methylcellulose will be evaluated and altered in experiments conducted within this report and a chemical cross-linker, developed from Jeffamine ED 2003 (O,O′-Bis(2-aminopropyl) polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol), will be created. Experimentation with these elements is outlined here, and will ultimately prompt future revisions and analysis.
ContributorsBundalo, Zoran Luka (Author) / Vernon, Brent (Thesis director) / LaBelle, Jeffrey (Committee member) / Overstreet, Derek (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
Revision hip procedures represent a large financial burden on hospitals and the problem will continue to worsen as the baby boomer generation ages and life expectancy goes up. The future problem is a complex issue that bridges scientific and anecdotal evidence and must be solved. A review of the current total hip arthroplasty procedure in regards to the physical properties of the materials used for hip prostheses is given. Revision procedures can be caused by infection or basic wear and tear from the stress that that implant is subjected to daily. Infections on these implants often present themselves as medical biofilms. The mechanisms of biofilm formation include a complex system of enzymes that work to initiate a phenotypic response based on an established quorum sensing within the colony of bacteria. Surgical methods to treat infection include irrigation and debridement as well as loading drug cement spacers with antimicrobial in hopes of delivering the antibiotic locally. Research is being done to better model the transport of drug through the tissue surrounding the implant, and will hopefully one day be available for use in individual patients.
ContributorsMcDermand, Matthew Paul (Author) / Caplan, Michael (Thesis director) / Vernon, Brent (Committee member) / McLemore, Ryan (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
Description
Cerebral aneurysms, also known as intracranial aneurysms, are sac-like lesions in the arteries of the brain that can rupture to cause subarachnoid hemorrhaging, damaging and killing brain cells. Metal coil embolization has been traditionally used to occlude and treat cerebral aneurysms to limited success, but polymer embolization has been suggested, because it can provide a greater fraction of occlusion. One such polymer with low cytotoxicity is poly(propylene glycol)diacrylate (PPODA) crosslinked via Michael-type addition with pentaerythritol tetrakis(3-mercaptopropionate) (QT). This study was performed to examine the behavior of PPODA-QT gel in vitro under pulsatile flow emulating physiological conditions. An idealized cerebral aneurysm flow model was designed based on geometries associated with an increase in rupture risk. Pressure was monitored at the apex of the aneurysm dome for varied flow rates and polymer filling fractions of 32.4, 78.2, and 100%. The results indicate that the amount of PPODA-QT deployed into the aneurysm decreases the peak-to-peak oscillation in pressure at the aneurysm wall by an inverse proportion. The 32.4 and 78.2% treatments did not significantly decrease the mean pressure applied to the aneurysm dome, but the 100% treatment greatly reduced it by diverting flow. This study indicates that the maximum filling fraction after swelling of PPODA-QT polymer should be deployed into the aneurysmal sac for treatment.
ContributorsWorkman, Christopher David (Author) / Vernon, Brent (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Biofilm derived orthopedic infections are increasingly common after contamination of an open bone fracture or the surgical site pre- and post-orthopedic prosthetic insertion or removal. These infections are usually difficult to eradicate due to the resistant nature of biofilms to antimicrobial therapy. Difficulty of treatment of biofilm derived infections is also partly due to the presence of persister cells in the biofilm matrix. Persister cells are tolerant to antimicrobial therapy delivered via the systemic route. It is thus possible for these cells to repopulate their environment once systemic antimicrobial delivery is discontinued. The antimicrobial concentration required to eradicate bacterial biofilms, minimum biofilm eradication concentration (MBEC), can be determined in vitro by exposing biofilms to different regimens of antimicrobial solutions. Previous studies have demonstrated that values of the MBEC vary depending on the material and surface the biofilm grows on. This study investigated the relationship between antimicrobial susceptibility and antimicrobial exposure time, and the effects of surface material type on the antimicrobial susceptibility of staphylococcal biofilms. It was concluded that antimicrobial susceptibility increases with increased antimicrobial exposure time, and that the investigated surface and material properties did not have an effect on the susceptibility of staphylococcal biofilms to antimicrobial therapy. Further investigation is however necessary to confirm these results due to some inconsistent data obtained over the course of the trials.
ContributorsTavaziva, Gamuchirai Clinton (Author) / Vernon, Brent (Thesis director) / Overstreet, Derek (Committee member) / Castaneda, Paulo (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
A self-stirring syringe pump was created in order to fill a void in the market for a medical device that could perform a lengthy drug infusion. This was accomplished by using a magnetic field mechanism that enclosed the body of a syringe. A stator was created in order to facilitate the induction of magnetic fields around the syringe body. A flexible magnetic stir bar was created to rotate within the syringe body while also being able to conform to the syringe plunder as an infusion occurred. In order for the stator with the syringe to fit onto a conventional syringe pump, a mount had to be made. This mount was removable to ensure easy access to the syringe once an infusion had occurred. A study was performed to determine whether or not the self-stirring syringe pump could keep a suspension homogenous over a lengthy infusion. It was found that the self-stirring syringe pump was able to accomplish this task.
ContributorsWitting, Avery Amadeus (Author) / Vernon, Brent (Thesis director) / Goryll, Michael (Committee member) / Faigel, Douglas (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Rupture of intracranial aneurysms causes a subarachnoid hemorrhage, which is often lethal health event. A minimally invasive method of solving this problem may involve a material, which can be administered as a liquid and then becomes a strong solid within minutes preventing flow of blood in the aneurysm. Here we report on the development of temperature responsive copolymers, which are deliverable through a microcatheter at body temperature and then rapidly cure to form a highly elastic hydrogel. To our knowledge, this is the first physical-and chemical-crosslinked hydrogel capable of rapid crosslinking at temperatures above the gel transition temperature. The polymer system, poly(N-isopropylacrylamide-co-cysteamine-co-Jeffamine® M-1000 acrylamide) and poly(ethylene glycol) diacrylate, was evaluated in wide-neck aneurysm flow models to evaluate the stability of the hydrogels. Investigation of this polymer system indicates that the Jeffamine® M-1000 causes the gels to retain water, resulting in gels that are initially weak and viscous, but become stronger and more elastic after chemical crosslinking.
ContributorsLee, Elizabeth Jean (Author) / Vernon, Brent (Thesis director) / Brennecka, Celeste (Committee member) / Overstreet, Derek (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2013-05
Description
The main goal of this project was to study and understand the release of gentamicin from in – situ, self – reactive drug delivery gelling matrix. The motivation behind this was to create a drug delivery mechanism for gentamicin and eliminate the need for re–injecting the drug multiple times into the patient. Gentamicin is used to treat various different bacterial infections of the central nervous system, blood, kidneys, gall bladder, bile duct, heart cavity linings, and heart valves. Pentaerythritol–tetrakis
(3 – mercaptoproprionate; QT) was crosslinked with poly(ethylene glycol) diacrylate (PEGDA) having an average molecular weight of 575 with the help of Phosphate Buffer Saline (PBS), with a buffer ionic strength of 0.143M and a pH of 8.9 and 11, for the drug concentrations of 5 mg/mL and 50 mg/mL, respectively. The Michael – type reaction formed the crosslinked self – administering gelling matrix. With the gelling matrix starting to coagulate into a hydrophobic solid in about 5 minutes, the material was injected into Tygon tubing. After complete solidification, the drug – loaded gels were extracted from the tubing and divided into 1 cm cylinders. The cylinders with 5mg/mL and 50mg/mL drug concentration exhibited a sustained and controlled release curve for about 288 hours. This project as well as this drug delivery system can in the future be expanded for use in the delivery of more hydrophobic long – term drugs to the patient.
ContributorsJolly, Nehal (Author) / Vernon, Brent (Thesis director) / Herman, Richard (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This study demonstrates that a polymer and drug conjugate can be tattooed onto tissue and deliver drug in a sustained manner. A number of polymers and drugs were investigated in this study in the aims of developing a formulation that could achieve sustained drug delivery for 1-2 weeks. The polymers selected for testing were PDLG 5004, PDLLA-Glycerol, and PEG-PLA, and the drugs used in conjunction with these polymers were rifampicin, moxifloxacin, and dexamethasone. Varying formulas containing these polymer and drug combinations were tattooed onto three different tissue types: bovine pericardial tissue, porcine corneal tissue, and porcine sclera tissue. The drug release rates from these tattoos were determined and characterized after studying the release for up to 20 days. The release rate of dexamethasone from both PDLG 5004 and PDLLA-Glycerol when tattooed onto bovine pericardial tissue demonstrated the best release rate of the formulations tested, with up to 14 days of sustained release. This preliminary research into tattoo-based, polymeric drug delivery is promising, and has the possibility to be developed into a beneficial form of ophthalmic drug delivery that could be expanded to other areas of treatment as well.
ContributorsKaplan, Serena Louise (Author) / Vernon, Brent (Thesis director) / Pathak, Chandrashekhar (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05