Medicine and Health Sciences Commons^™

Polymeric Chloroquine In Metastatic Pancreatic Cancer Therapy, Rubayat Islam Khan

Theses & Dissertations

Hydroxychloroquine (HCQ) is an established drug that has been used for the treatment of multiple diseases, including malaria, rheumatoid arthritis, and lupus erythematosus. Several recently published studies have highlighted its beneficial use in various types of cancers, and a plethora of clinical trials are currently evaluating its use in cancer therapies, wherein some of the results look promising. The preclinical studies to date suggest HCQ can work effectively in conjunction with traditional cancer treatments, as it has been shown to sensitize tumor cells to a wide range of chemotherapeutic agents. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has …

Evaluation Of Medication Optimization In The Setting Of Ecmo Therapy: Assessment Of Therapeutic Effectiveness, Greg Peitz

Theses & Dissertations

A series of studies within the setting of extracorporeal membrane oxygenation (ECMO) was undertaken to specifically answer questions related to medication optimization during this complex therapy. These studies included medication therapies involving optimal anticoagulation, analgesia delivery, fluid resuscitation, and infection related outcomes in the context of ECMO. Each investigation was retrospective in nature and included patients from a single institution. The results of these studies indicated the following: 1.) various anticoagulation goals do not impact severe, life-threatening bleeding events during ECMO therapy; 2.) sepsis is a common occurrence in the setting of ECMO; 3.) the choice of either a crystalloid …

Applications Of Population Pharmacokinetic Modeling In People Living With Hiv, Michelle M. Pham

Theses & Dissertations

Population pharmacokinetic modeling has become an important tool for the individualization of medicine in HIV care and clinical pharmacology in general. This dissertation explores many applications of population pharmacokinetic modeling to help identify drug exposure, drug-drug interactions, and sources of variability in populations living with HIV. Comprehensive HIV care involves simultaneous treatment of the disease and any co-infection and/or co-conditions.

The first objective was to identify potential drug-drug interactions affecting combination antiretroviral therapy (ART) consisting of efavirenz, tenofovir disoproxil fumarate and emtricitabine, from concomitant use of chemotherapy agents. Three models were developed with sparse sampling to characterize efavirenz, emtricitabine, and …

The Development And In Vivo Immunologic Assessment Of Biodegradable Microparticles Incorporating Cpdi-02 And Mucosal Protein Vaccine, Jacob E. Parriott

Theses & Dissertations

Encapsulation in biodegradable microparticles (MPs) is a promising approach to increase the efficacy of intranasally administered protein vaccines. The generation of long-lived adaptive immune responses against encapsulated protein vaccines, however, requires the incorporation of a suitable mucosal adjuvant. CPDI-02—a complement peptide-derived immunostimulant that selectively activates dendritic cells and macrophages over neutrophils while minimizing the inflammatory side effects of parent C5a—has previously been incorporated into both systemic and mucosal vaccine formulations via direct conjugation to chemical moieties, peptides, proteins, inactivated pathogens, and the surface of biodegradable particles, to enhance Th1-biased cellular immune responses. The effect of CPDI-02 surface conjugation to MPs …

Biologically-Inspired Nanoparticles For Oncology Applications, Aishwarya Bapat

Theses & Dissertations

Cancer is the leading cause of death in the United States and its high mortality rate can be attributed towards poor diagnosis methods and less effective therapeutic treatments. Many nanotechnology-based diagnostics and therapeutics are being developed to improve cancer patient outcomes. In this work, we have studied nanoparticles for diagnostic and therapeutic applications in cancer treatment.

In the first work, novel fluorescent NPs loaded with indocyanine green (ICG) were developed for bioimaging applications of pancreatic cancer. Targeted fluorescent nanoparticles (NPs) are being developed to image a range of cancer types with the goal to improve patient outcomes by utilizing in …

Design, Synthesis, And Biological Investigation Of Pyridine Sulfones As Anti-Chlamydia Trachomatis Agents, Mohamed A. Seleem

Theses & Dissertations

Chlamydia trachomatis is the most prominent cause of sexually transmitted bacterial infections worldwide, with around 128 million reported cases annually. This pathogen can cause severe urogenital and ocular consequences, resulting in infertility and trachoma. In its unique developmental cycle, Chlamydia fluctuates between two distinct forms, elementary bodies (EBs) and reticulate bodies (RBs). We hypothesized that caseinolytic protease P (ClpP), a conserved protease among bacterial species, drives the Chlamydia developmental cycle. Earlier work by the Ouellette group demonstrated that Chlamydia relies on its ClpP2 paralogue (ctClpP2) to differentiate between its developmental forms. Dysregulation of ctClpP2 had a significant …

Modulation Of Immune Homeostasis In Neurodegenerative Diseases, Pravin Yeapuri

Theses & Dissertations

Modulating the immune system via. transformation of CD4+ T cell effector to regulatory (Teff to Treg) or promoting microglial clearance of abnormal disease proteins are attractive therapeutic strategies to restore immunological balance in neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD). In the past decade, we defined a safe and effective pathway for Treg induction through the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was developed in PD animal models and early phase I human studies demonstrating proof-of-concept efficacy for ameliorating disease signs and symptoms. Despite the recorded efficacy, the medicine’s short half-life, limited bioavailability, and injection site reactions …

Polymeric Nanocarriers For Delivery Of Small Molecules Inhibiting Tubulin Polymerization For The Treatment Of Pancreatic Cancer And Lung Metastatic Melanoma, Rajan Sharma Bhattarai

Theses & Dissertations

The aim of this thesis is to develop delivery systems for the novel small molecules which inhibit tubulin polymerization. One of the small molecules was modified to lipid conjugate to increase the lipophilicity of the molecules which in turn drastically improved the drug loading in amphiphilic polymeric system. The second molecule was conjugated to the amphiphilic polymeric backbone with pH sensitive Schiff’s linker for the tumor site specific delivery in lung metastatic melanoma model.

Chapter 1 discusses the tumor microenvironment for the solid tumor especially focusing on Pancreatic Ductal Adenocarcinoma (PDAC). Further the drug delivery system currently researched for addressing …

The Development Of Thermoresponsive Hydrogel-Based Drug Delivery Systems For The Treatment Of Musculoskeletal Diseases, Ningrong Chen

Theses & Dissertations

Water-soluble polymers are one of the most commonly used drug delivery vehicles for musculoskeletal diseases. During the past few decades, various biocompatible polymers have been employed in the development of thermoresponsive hydrogels as drug delivery systems for the treatment of local musculoskeletal pathologies. As part of our laboratory’s contribution to this field of study, I have successfully developed three thermoresponsive hydrogel-based formulations for the treatment of three different pathologies associated with the musculoskeletal system.

As my initial effort, I have developed a bone-targeting injectable hydrogel drug delivery system based on Pluronic 127 (Poloxamer 407), which is a Generally Recognized As …

Development Of Bioactive Polymers For Anticancer Sirna Therapy, Siyuan Tang

Theses & Dissertations

Pancreatic ductal adenocarcinoma is a deadly disease with limited treatment options due to late diagnosis and resistance to conventional chemotherapy. Moreover, with the decreased survival rate in the past several years, pancreatic cancer may become the second leading cause of cancer-related death by surpassing breast cancer in 2030. CXCR4/CXCL12 pathway is crucial in tumor-supporting microenvironment, tumor progression, angiogenesis, metastasis and chemotherapy resistance. Small interfering RNA (siRNA) is one of the interfering RNA (RNAi), which targets mRNA specifically then knockdowns the overexpressed oncogene. Thus, siRNA has been widely used as a therapeutic strategy for various diseases including PDAC. In the research …