Medicine and Health Sciences Commons^™

Patient Satisfaction With Substance Use Disorder Rehabilitation Services, Trupti Dhumal

Electronic Theses and Dissertations

Background: Patient satisfaction is considered as an important indicator in the evaluation of healthcare quality across an array of treatments and services. It is deemed vital especially in the field of substance use disorder (SUD) research due to an increased emphasis on understanding patients’ perceptions regarding their treatment and the attributes that drive their progress towards recovery. Despite the potential value, gaps have been recognized in the exploration of these satisfaction-related assessments among patients undergoing SUD treatment in residential rehabilitative settings. Thus, there is a need for understanding the dimensions contributing to satisfaction which would facilitate the development of …

Design, Synthesis, & Biological Evaluation Of Novel Het-Aromatic/Aromatic Analogs For The Treatment Of Hiv, Cancer, & Cognitive Dysfunctions, Mohit Gupta

Electronic Theses and Dissertations

Cyclophilin A are a class of peptidyl-prolyl isomerases that catalyzes isomerization of the proline residue within a protein. Cyclophilin A plays an instrumental role in the pathogenesis of HIV and HCV virus. Using structure-based drug we designed and synthesized small molecule inhibitors of cyclophilin A. These inhibitors were biologically evaluated for their ability to inhibit WT HIV-1 inhibition.

Mitogen-Activated Protein Kinase signaling cascades plays a critical role in cancer cell survival, metastasis, and chemo-resistance. The MEK5/ERK5 pathway, which is a member of MAPK signaling cascade, is involved in cell survival, anti-apoptotic signaling, angiogenesis, and cell motility. It is found to …

Structure Elucidation Of A Pyrrolobenzodiazepine Alkaloid And A Biologically Active Polyketide Produced By Rhodococcus Sp. Mtm3w5.2 Via Two-Dimensional Nmr Spectroscopy, Garrett Johnson

Electronic Theses and Dissertations

As the battle against ever-increasing drug resistence bacteria rages on, novel and sometimes more complex natural products can be used to combat this. In this study, two-dimensional NMR techniques were utilized to collect a complete spectral data set for two natural products. The first structure, a synthesized Pyrrolobenzodiazepine alkaloid natural product was confirmed through these methods. The second, a strain of Rhodococcus, MTM3W5.2, produces a novel antibacterial molecule in broth cultures and the active compound was fractionated using a Sephedex LH-20 column. Chromatographic purification yielded a pure sample at 58.90 minutes, RT.58. HRMS data deduced an exact mass of …

A Recombinant Cholera Toxin B Subunit Variant (Ctb-Kdel) Exhibits Unique Colon Mucosal Healing Effects That Have Therapeutic Implications For Inflammatory Bowel Disease., Joshua Mark Royal

Electronic Theses and Dissertations

This dissertation uncovers the mechanism and explores the utility of a recombinant cholera toxin B subunit (CTB) variant containing a KDEL endoplasmic reticulum (ER) retention motif (CTB-KDEL) as a drug candidate for the treatment of inflammatory bowel disease (IBD). CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Here, we reveal …

A Quantitative Study Of Drug Recrystallization In Drug-In-Adhesive Transdermal Patches Using Vibrational Spectroscopy, Yi Li

Electronic Theses and Dissertations

Drug-in-adhesive (DIA) transdermal patches are an important type of transdermal drug delivery system (TDDS). The drugs used in the DIA system are frequently present in metastable forms, such as amorphous solids or supercooled liquids. These drug states are thermodynamically unstable and tend to undergo recrystallization. Recrystallization of the active pharmaceutical ingredient can adversely affect the efficacy of transdermal products. This dissertation demonstrates a systematic approach to quantify the crystalline content of the API in DIA systems. This approach uses a novel method of preparing calibration standards and a spectroscopic method to reliably predict crystalline content in DIA patches. Spectroscopic tools, …

Dual Inhibition Of The Pi3k/Akt And Mek5/Erk5 Pathways For The Treatment Of Breast Cancer, Thomas Douglas Wright

Electronic Theses and Dissertations

Breast cancer is a heterogeneous disease state with several challenging frontiers. In particular, aberrations in the Phosphoinositide-3-kinase (PI3K) and Mitogen Activated Protein Kinase (MAPK) pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. New evidence suggests that MEK5/ERK5, a member of the MAPK family, is a crucial component in the proliferation and survival of several aggressive cancers. We hypothesize that inhibiting both PI3K/Akt and MEK5/ERK5 pathways will decrease cell viability while maintaining limited collateral toxicity. In this study, we examined the effects …

Design And Synthesis Of Pyrimidine Based Heterocycles As Potential Anti-Cancer Agents With Combination Chemotherapeutic Potential Or Targeted One Carbon Metabolism Inhibition And Anti-Opportunistic Agents, Arpit Doshi

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic, bicyclic and tricyclic pyrimidine-based heterocycles as a) single agents with combination chemotherapy potential having dual antiangiogenic effects and cytotoxic effects or b) one-carbon metabolism inhibitors for targeted tumor therapy; or c) selective Pneumocystis jirovecii (pj) dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization or thymidylate synthase as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), epidermal growth …

The Development Of Hybrid Process Control Systems For Fluidized Bed Pellet Coating Processes, Hanzhou Feng

Electronic Theses and Dissertations

The conventional basic control for pharmaceutical batch processes has several drawbacks. The basic control often uses constant process settings discovered by trial and error. The rigid process operation provides limited process understanding and forgoes the opportunities of process optimization. Product quality attributes are measured by the low efficient off-line tests, therefore these cannot be used to monitor and inform the process to make appropriate adjustments. Frequent reprocessing and batch failures are possible consequences if the process is not under effective control. These issues raise serious concerns of the process capability of a pharmaceutical manufacturing process.

An alternative process control strategy …

Modeling And Prediction Of Amorphous Solid Dispersion Formation Using A Molecular Descriptor, Kevin Deboyace

Electronic Theses and Dissertations

Poor aqueous solubility of an active pharmaceutical ingredient (API) is a significant hurdle during drug development. Delivering a drug in its amorphous solid-state is a potential method to overcome this issue, since the amorphous form has increased apparent aqueous solubility. However, the amorphous state is only metastable, and is thermodynamically driven to recrystallize. As a result, pure amorphous drugs are seldom used in marketed products. Intimately mixing a drug in its amorphous form with a polymer, known as an amorphous solid dispersion (ASD), has the potential to significantly extend the physical stability of the amorphous form, while maintaining the benefit …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Development Of A Novel Nanotechnology-Based Vaccine Adjuvant And Delivery System For Systemic And Mucosal Immunity, Mohammed Ali Bakkari

Electronic Theses and Dissertations

Many serious infections for which there are no existing vaccines, enter by a mucosal route such as HIV, influenza, and tuberculosis, etc. Therefore, designing safe and effective mucosal vaccines that elicit robust immune response at mucosal sites is still a major challenge without a safe mucosal adjuvant. Previously, our laboratory had discovered inulin acetate as a novel toll-like-receptor-4 agonist (adjuvant). The study in this dissertation explored the application of nanoparticles prepared with inulin acetate (InAc-NPs) as a vaccine adjuvant and delivery system for enhancing mucosal immunity. The rationale behind selecting InAc-NPs is their proven ability to activate strong systemic immunity …

Design, Synthesis, And Evaluation Of Gunw-3 As A Brain Targeting Agent, Asim Najmi

Electronic Theses and Dissertations

The blood brain barrier (BBB) is a barrier in the brain that separates the peripheral blood circulation system from the central nerve system (CNS). The barrier effectively protects the brain from xenobiotics. The BBB serves as a physical barrier through the tight junction of endothelial cells that were found to be 50-100 times tighter than that of normal endothelial cells. Different drug efflux pumps such as P-glycoproteins and multidrug-resistance proteins are found to be overdistributed on the BBB. These drug efflux pumps help pump xenobiotics out if they enter the cells and serv as an additional mechanism to prevent xenobiotics …

Thiol Specific Fluorogenic Agents For Live Cell Subcellular Organelle Thiol Imaging, Yahya Alqahtani

Electronic Theses and Dissertations

Thiols or sulfhydryl groups (-SH) play a significant role in protein structures and functions. The unique properties of a thiol group are the basis for its roles in cellular functions. Structurally, thiols are divided into protein thiols (PSH) and non-protein thiols (NPSH). NPSH include glutathione, cysteine, and homocysteine. Thiols are distributed in an uneven manner in the cell and subcellular organelles. Disturbance of thiol levels has been associated with serious diseases such as cancer, aging, cardiovascular diseases, Alzheimer disease, liver damage, and edema. The significant roles of thiols in the biological system have stimulated the development of various approaches to …

Formulation Development, Preclinical Testing, And Primary Packaging Optimization For Cannabinoids And Other Therapeutics, Pranjal Taskar

Electronic Theses and Dissertations

Through the process of drug development, a molecule goes through discovery screening; lead selection and optimization, ADME testing, toxicity profiling, dosage form determination, preclinical testing in an in vitro and in vivo setup, folloby clinical research, FDA review and approval until eventually it is manufactured in the determined dosage form and reaches the patient. At every point through this process, scientists actively work towards a smoother transition and a quick and safe approval of the molecule towards the next step. The different chapters in this research would cover various phases of drug development; from discovery stage to fill-finish and primary …

Role Of Cardiolipin Remodeling In The Malignant Progression Of Breast Cancer, Jawaher H. Alkhamisy

Electronic Theses and Dissertations

In spite of the current advances in both radiotherapy and surgical techniques as well as molecularly targeted therapies, over 90 percent of cancer mortality rate is due to metastases. Considering the pivotal role of metabolism in cellular physiology, there is no doubt that metabolic alterations are critical for metastatic progression. Cardiolipin (CL), the signature phospholipid of mitochondria, is linked to a variety of vital mitochondrial processes, like oxidative phosphorylation. Cardiolipin is a unique dimeric phospholipid which contains four fatty acyl chains. Moreover, the CL remodeling process is believed to be responsible for generation of immature CL species that contribute to …

Development Of Controlled Release Oral Dosages By Density Gradient Modification Using 3d Printing Technologies, Zhiqing Hu

Electronic Theses and Dissertations

Over the years, three-dimensional (3D) printing has gradually become more comin people's lives. Due to its quick development, it has attracted the attention of researchers in the pharmaceutical industry. The main purpose of this project was to couple fused deposition modelling (FDM) 3D printing with hot melt extrusion (HME) technology to manufacture tablets with different drug release profiles and to solve dose issues related to an individual’s physiological differences and to enhance extended release properties. Ketoprofen was used as the model drug and different properties were added to the polymer to create a formulation suited to HME technology for the …

Development Of Tissue-Derived Biomaterial ‘Cornea-Ecmix’: Its Utility In The Management Of Corneal Diseases, Somshuvra Bhattacharya

Electronic Theses and Dissertations

Transparent cornea, at the front of the eye, mediates vision by refracting incoming light. Due to its anatomical position, cornea is susceptible to a variety of physical and chemical insults. Severe damage caused to cornea due to trauma or disease conditions can impair vision. While the cornea’s inherent repair mechanism restores partial vision loss, transplantation is the only viable treatment option if its transparency is completely lost. A global shortage of transplantable donor tissues necessitates the need for the development of functional corneal prosthetics. As cornea mostly is made up of extracellular matrix (ECM), several studies have explored the utility …

Localized Transdermal Delivery Of Chemopreventive Agents To The Breast, Abdulsalam Alqahtani

Electronic Theses and Dissertations

Breast cancer is the second leading cause of cancer death in women. About 1 in 8 women will develop breast cancer in their lifetime. The current systemic approaches are associated with significant side effects including some life-threatening toxicity, leading to poor patient compliance. To overcome this limitation, localized transdermal drug delivery system was investigated in the current study. In addition, majority of breast cancers originate from the ducts and lobules in the breast. Therefore, localized transdermal drug delivery system can maximize drug concentration in the breast and minimize systemic adverse effects, resulting in a potential approach for preventing and/or treating …

Nutritional Transporter Mediated Drug Delivery For Cancer, Siddharth S. Kesharwani

Electronic Theses and Dissertations

Recent advancements in nanotechnology have unfolded novel opportunities in medicine, especially in targeted therapeutics and imaging for cancer. However, the majority of the existing nanotechnologies for cancer suffer from shortcomings such as (i) rapid elimination from the systemic circulation before reaching the cancer tissue. (ii) poor tumor accumulation, targeting, and penetration due to inadequate vasculature and extensive extracellular matrix in the tumor. Thus, overcoming these two limitations of nanotechnology is of considerable interests for cancer researchers. In this dissertation, we demonstrate the feasibility of glucose-modified nanoparticles (GLU-NPs) as an efficient cancer targeted-delivery system for enhancing the systemic circulation time and …

Long-Acting Intraductal Drug Delivery Systems For The Breast, Mibin Joseph

Electronic Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer in women in the US. Ductal carcinoma in situ (DCIS) is a premalignant lesion that has not metastasized through the regional lymph nodes to other organs. Currently, all breast cancers including localized breast cancers are treated with the same aggressive therapy. Localized drug delivery by direct intraductal injections into the mammary ducts can achieve high drug concentration at the target site. However, poor retention of drugs in the ducts limits the successful translation of this approach to the clinic. To this end, the main goal of this dissertation is to develop …

Progress Toward The Synthesis Of 3-Methoxyflavones As Potential Antioxidants, Neuroprotective Agents, And Trifluoromethylated 19f Nmr Probes, Reem Alkhodier

Electronic Theses and Dissertations

The total synthesis of polyhydroxylated flavones have proven to be challenging, due to the presence of more than one hydroxyl group. Direct cyclization was not successful in any of the attempts. However, by using a silyl protecting group, the cyclization was feasible. Other reactions like the Friedel-Crafts acylation and selective protection of phenols were also difficult.

Nanosuspension Based Electrolyte Sensitive In Situ Gel For Topical Ocular Delivery Of Natamycin, Poorva H. Joshi

Electronic Theses and Dissertations

Natamycin (NT) is a commercially available antifungal drug used for the treatment of fungal keratitis, an infection which affects the clear corneal surface and its associated layers. Currently, NT is available commercially as a 5% w/v ophthalmic suspension, to be administered topically. The main objective of the present investigation was to develop and evaluate the natamycin loaded nanosuspension (NT-NS), as well as it’s corresponding in-situ gel (NT-NS-GG), for the treatment of fungal keratitis. NT-NS was prepared using homogenization technique and optimized based on size, PDI, zeta potential (ZP), assay and process stability. Further, optimized NT-NS was modified into an in-situ …

Pegylated Nanostructured Lipid Carries For Amphotericin B Ocular Delivery, Prit Manish Lakhani

Electronic Theses and Dissertations

The Chapter II focuses on formulation of an optimized and robust amphotericin B ocular formulation with prolonged precorneal residence and ocular tissue concentration at par or superior to the marketed preparations. Additionally, demonstrating stability of amphotericin B formulations in presence of preservative in comparison to marketed preparation, making it an ideal choice of formulation for multi-dosing. As mentioned earlier, we optimized PEGylated nanostructured lipid carriers (PEG-NLC-AmB) for ocular delivery of amphotericin B. The formulations could be autoclaved with at least one-month stability and in vivo ocular biodistribution was statistically insignificantly different compared to AmBisome®. To accomplish the aim, strategies such …

In-Situ Gel Of Cyclosporine A – Loaded Solid Lipid Nanoparticles For Topical Occular Delivery For Dry Eye Disease, Samir Shyambabu Senapati

Electronic Theses and Dissertations

Cyclosporine (CSA) is a highly potent immunosuppressant drug and has been used to treat rheumatoid arthritis, psoriasis, organ rejection post-transplant, and chronic dry eye disease. The objective of this investigation was to increase the CSA residence time on the ocular surface using solid lipid nanoparticles (SLNs) and its in-situ gel formulation (CSA-SLN-IG), for treatment of dry eye disease. CSA loaded SLNs (CSA-SLN) were prepared with the homogenization method, using Precirol ® ATO 5 as a solid lipid and Tween® 80 and Poloxamer 188 as surfactants. Prepared SLNs were optimized based on particle size, zeta potential (ZP), PDI, assay and stability. …

Optimization And Characterization Of Hot-Melt Extruded Anti-Inflammatory And Local Anesthetic Bio-Adhesive Semisolid Formulation Using Design Of Experiments (Doe), Rishi Chinmay Thakkar

Electronic Theses and Dissertations

Hot melt extrusion is a versatile continuous manufacturing process extensively investigated for its applications with production of oral solid dosage forms, the aim of this study was to venture the applicability of HME in continuous manufacturing of topical semi-solid ointment formulations. Novel combination of a topical corticosteroid (Triamcinolone Acetonide) and local anesthetic (Lidocaine hydrochloride) were selected to be formulated with a water-soluble ointment base consisting of PEG 4000, PEG 1500 and Propylene glycol after performing appropriate drug-excipient compatibility studies. To determine the ratios of the solid to liquid components of the macrogol base, ‘quality by design’ approach was employed by …

Comparative Effectiveness And Safety Of Non-Vitamin K Antagonists Oral Anticoagulants And Warfarin In Elderly Patients With Non-Valvular Atrial Fibrillation And Diabetes, Siddhi Korgaonkar

Electronic Theses and Dissertations

Results: The matched sample consisted of 4578 patients (2291 in each group). NOACs were found to significantly reduce the risk of stroke/SE compared to warfarin (Hazard Ratio (HR): 0.373, 95% confidence interval (CI): 0.247 - 0.564, p<0.001); but, no significant difference was seen between NOACs and warfarin in terms of reducing the risk of MI (HR: 0.864, CI: 0.594 – 1.257, p=0.446). NOACs were found to significantly reduce the risk of ICH (HR: 0.500, CI: 0.300 – 0.834, p=0.008) and OB (HR: 0.608, CI: 0.424 – 0.870, p=0.007); but no difference was seen in the risk of MGB (HR: 0.862, CI: 0.640 – 1.160, p=0.326) between NOACs and warfarin. NOACs were also found to reduce the risk of all-cause mortality (HR: 0.783, CI:0.656 – 0.873, p=0.007). The composite of effectiveness and safety outcomes, and all-cause mortality was statistically significant proving superior overall effectiveness and safety of NOAC therapy to warfarin therapy in terms of risk reduction (HR:0.685, CI:0.587 – 0.801, p<0.001).

Pharmacy Value-Based Incentive Programs: An Evaluation Of Health Plan Strategies, Pharmacist Attitudes, And Financial Impact On Retail Stores, Tristen H. Jackson

Electronic Theses and Dissertations

Since the Affordable Care Act (ACA) in 2012 health plans serving Medicare beneficiaries have begun receiving sizeable incentives (>$1B) for demonstrating high ratings to quality performance scores in CMS’s Medicare star ratings program. Several of the quality measures can be directly impacted by retail pharmacists (e.g. medication adherence measures) resulting in health plans implementing programs designed to incentive retail pharmacies to work toward improving their own performance related to quality measures. While awareness of these value-based incentive (VBI) programs is growing there is still a significant lack of research which elucidates the nature of these programs and the potential …

Safety Constraint Optimization Of Combination Drug Therapy In Hypertension Clinical Trials, Victor Chukwu

Electronic Theses and Dissertations

In Clinical Practice, combination drug therapy has become common in treating many disease conditions. The purpose of these combinations is often to ensure optimal efficacy and to reduce adverse effects that may arise from monotherapy. Clinical trials have also been conducted to ensure efficacy and safety of these combinations before they are introduced into the market. However, adverse effects still occur with combination therapies. The objective of this study is to (1) To determine a region of optimum doses of Drug A and Drug B in combination while focusing on efficacy alone (2) To determine a region of optimum doses …

Synthesis Of N-Heterocyclic Molecules And Their Applicability Towards Ion Sensing: Polymeric Chemosensors, Aikohi M. Ugboya

Electronic Theses and Dissertations

Critical to biological and environmental processes are anions because often times their relative concentration in our body can be an indicator of one’s well-being. Therefore, highly sensitive and cost-efficient methods for ions recognition is necessary for human health. In recent times, polymeric chemosensors have become a vital tool for sensing ions because of its higher sensitivity and good mechanical properties compared to their monomeric counterparts. These sensors are designed to produce a measurable response in the presence of a targeted ion such as an electrochemical or optical signal. The unique structure and the photophysical properties of the 1,2,3-triazole core coupled …

Development And Characterization Of Sustained-Release Formulations Via Novel Hot Melt Extrusion Techniques, Bjad Khalaf Almutairy

Electronic Theses and Dissertations

Hot melt extrusion (HME) is a leading technology that can be applied to many pharmaceutical preparations as solid dispersions. Part of this research project focus on injecting pressurized carbon dioxide (P-CO2) gas during the HME process. These combined techniques have an additional advantage of being adaptable and portable to a hot melt extruder instrument. The use of HME alongside with other techniques (P-CO2 or co extrusion process) for preparing an improved controlled/sustained release formulation is the main theme of this research project. Current research focusing on Active Pharmaceutical Ingredients (APIs) with good aqueous solubility requires novel approach to obtain tailored …