Matching Items (6)
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- All Subjects: Drug Delivery
- All Subjects: Kenya
- Creators: Caplan, Michael
Description
Sickle cell disease is a genetic disorder that can cause substantial helath problems. It is the result of a mutation in the DNA coding for hemoglobin. As a result of changes in two important amino acids, a person suffering from sickle cell disease will have erythrocytes that do not maintain the typical biconcave shape and instead for a crescent shape. Individuals with sickle cell disease may have many health problems tied to their irregular hemoglobin. The unusual shape of the erythrocytes leads to a much shorter cell life, which means that even though bone marrow remains active long past childhood to try to keep up with the loss of erythrocytes, the body is still unable to accommodate the rapid death of erythrocytes. The malformed erythrocytes can also cause vascular occlusion, blocking blood vessels and slowing blood flow. While sickle cell disease has the potential to spread worldwide, it is particularly common in Africa. This may be because people with the sickle cell trait have a high resistance to malaria, making them more likely to survive that ubiquitous disease and pass on their traits to their offspring. However, the mortality rate in young children with sickle cell disease is very high, in part because the spleen, already stressed by filtering out dead erythrocytes, has difficulties filtering out bacteria. One of the keys to stopping the spread of the disease is neonatal screening, but this requires specialized equipment that is fairly uncommon in rural areas, as can be seen in Kenya. Therefore, it would be highly beneficial to develop a more cost-effective and widely available method for testing for sickle cell disease.
ContributorsWold, John (Author) / Caplan, Michael (Thesis director) / LaBelle, Jeffrey (Committee member) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
Diabetes is a growing epidemic in developing countries, specifically in rural Kenya. In addition to the high cost of glucose testing, many diabetics in Kenya do not understand the importance of testing their blood glucose, let alone the nature of the disease. This project addresses the insufficiency of educational materials regarding diabetes in rural Kenya. The resulting documents can easily be adjusted for use in other developing countries.
ContributorsBuchak, Jacqueline (Author) / Caplan, Michael (Thesis director) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Imaging analysis of local drug delivery is important because in both studies involving chemotherapy targeted toward glioblastoma and antimicrobial addressing infection, the drug concentration and distribution are unknown. There are a variety of studies focused on the local delivery of drug to a targeted location, but we are presenting a way of quantifying the concentration of the drug and the distribution of the drug during a period of time. This study aims to do that by utilizing Materialise Mimics to analyze the MRI images of local drug delivery in glioblastoma in canines and antimicrobial gel in rabbit femurs. The focus of the technique is to register the anatomy in T1-weighted spin echo images to the drug delivery in T2 flow attenuated inversion recovery (FLAIR) images in order to see where the drug went and did not go relative to the anatomical part. Both studies focus on addressing effective volumes of drug to a designated anatomical area, in which the delivery can be difficult as it involves bypassing the blood brain barrier in the first study and achieving effective volumes while preventing toxicity to the kidneys in the second study. The goal of this project lies in determining the drug volumes and location for the specified duration and anatomical part.
ContributorsJehng, Hope (Author) / Caplan, Michael (Thesis director) / Sirianni, Rachael (Committee member) / Chemical Engineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Annually, approximately 1.7 million people suffer a traumatic brain injury (TBI) in the United States. After initial insult, a TBI persists as a series of molecular and cellular events that lead to cognitive and motor deficits which have no treatment. In addition, the injured brain activates the regenerative niches of the adult brain presumably to reduce damage. The subventricular zone (SVZ) niche contains neural progenitor cells (NPCs) that generate astrocytes, oligodendrocyte, and neuroblasts. Following TBI, the injury microenvironment secretes signaling molecules like stromal cell derived factor-1a (SDF-1a). SDF-1a gradients from the injury contribute to the redirection of neuroblasts from the SVZ towards the lesion which may differentiate into neurons and integrate into existing circuitry. This repair mechanism is transient and does not lead to complete recovery of damaged tissue. Further, the mechanism by which SDF-1a gradients reach SVZ cells is not fully understood. To prolong NPC recruitment to the injured brain, exogenous SDF-1a delivery strategies have been employed. Increases in cell recruitment following stroke, spinal cord injury, and TBI have been demonstrated following SDF-1a delivery. Exogenous delivery of SDF-1a is limited by its 28-minute half-life and clearance from the injury microenvironment. Biomaterials-based delivery improves stability of molecules like SDF-1a and offer control of its release.
This dissertation investigates SDF-1a delivery strategies for neural regeneration in three ways: 1) elucidating the mechanisms of spatiotemporal SDF-1a signaling across the brain, 2) developing a tunable biomaterials system for SDF-1a delivery to the brain, 3) investigating SDF-1a delivery on SVZ-derived cell migration following TBI. Using in vitro, in vivo, and in silico analyses, autocrine/paracrine signaling was necessary to produce SDF-1a gradients in the brain. Native cell types engaged in autocrine/paracrine signaling. A microfluidics device generated injectable hyaluronic-based microgels that released SDF-1a peptide via enzymatic cleavage. Microgels (±SDF-1a peptide) were injected 7 days post-TBI in a mouse model and evaluated for NPC migration 7 days later using immunohistochemistry. Initial staining suggested complex presence of astrocytes, NPCs, and neuroblasts throughout the frontoparietal cortex.
Advancement of chemokine delivery was demonstrated by uncovering endogenous chemokine propagation in the brain, generating new approaches to maximize chemokine-based neural regeneration.
ContributorsHickey, Kassondra (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Holloway, Julianne (Committee member) / Caplan, Michael (Committee member) / Brafman, David (Committee member) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2021
Description
Achieving effective drug concentrations within the central nervous system (CNS) remains one of the greatest challenges for the treatment of brain tumors. The presence of the blood-brain barrier and blood-spinal cord barrier severely restricts the blood-to-CNS entry of nearly all systemically administered therapeutics, often leading to the development of peripheral toxicities before a treatment benefit is observed. To circumvent systemic barriers, intrathecal (IT) injection of therapeutics directly into the cerebrospinal fluid (CSF) surrounding the brain and spinal cord has been used as an alternative administration route; however, its widespread translation to the clinic has been hindered by poor drug pharmacokinetics (PK), including rapid clearance, inadequate distribution, as well as toxicity. One strategy to overcome the limitations of free drug PK and improve drug efficacy is to encapsulate drug within nanoparticles (NP), which solubilize hydrophobic molecules for sustained release in physiological environments. In this thesis, we will develop NP delivery strategies for brain tumor therapy in two model systems: glioblastoma (GBM), the most common and deadly malignant primary brain tumor, and medulloblastoma, the most common pediatric brain tumor. In the first research chapter, we developed 120 nm poly(lactic acid-co-glycolic acid) NPs encapsulating the chemotherapy, camptothecin, for intravenous delivery to GBM. NP encapsulation of camptothecin was shown to reduce the drug’s toxicity and enable effective delivery to orthotopic GBM. To build off the success of intravenous NP, the second research chapter explored the utility of 100 nm PEGylated NPs for use with IT administration. Using in vivo imaging and ex vivo tissue slices, we found the NPs were rapidly transported by the convective forces of the CSF along the entire neuraxis and were retained for over 3 weeks. Based on their wide spread delivery and prolonged circulation, we examine the ability of the NPs to localize with tumor lesions in a leptomeningeal metastasis (LM) model of medulloblastoma. NPs administered to LM bearing mice were shown to penetrate into LM mets seeded within the meninges around the brain. These data show the potential to translate our success with intravenous NPs for GBM to improve IT chemotherapy delivery to LM.
ContributorsHouseholder, Kyle Thomas (Author) / Sirianni, Rachael W. (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Caplan, Michael (Committee member) / Wechsler-Reya, Robert (Committee member) / Arizona State University (Publisher)
Created2018
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 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