Digital Commons Network^™

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 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 …

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 …

Evaluation Of The Effect Of Carvedilol On The Thioredoxin Pathway In H9c2 Rat Cardiomyocytes, Metab Alharbi

Electronic Theses and Dissertations

The thioredoxin (Trx) system is an endogenous antioxidant system that affects cell function and survival through controlling cellular redox status. Trx and TrxR are the main enzymes in this system while thioredoxin interacting protein (TXNIP) is a negative regulator. This study’s goal was to better understand the Trx system’s involvement in the cardiovascular disease and modulate the pathway through drug treatment. Carvedilol is a non-selective β-blocker that also exhibits antioxidant properties, but the exact mechanism of the antioxidant effect is still unclear. H9c2 rat cardiomyocytes were used to examine the effect of carvedilol on the Trx system under normal conditions. …

Development Of Topical Oil/Peg Creams Of Voriconazole, Abhishek Shivashankar Shettar

Electronic Theses and Dissertations

Voriconazole (VRC) was selected as a model drug for preparation of Oil/PEG cream consisting of PEG 2000, PEG 400 and propylene glycol after performing drug-excipient compatibility studies. Twin screw processor with a 10 mm co-rotating twin screw configuration was used for preparation of oil/PEG creams. Creams prepared using twin-screw processor were characterized for the following: Differential Scanning Calorimetry (DSC), pH, Solvent activity (as)), viscosity, drug content uniformity, in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) using human cadaver skin. Creams are heterogenous biphasic semi-solid preparations consisting of oil and aqueous phases, wherein one phase is dispersed …

Synthesis Of Fluoroflavones As Potential Neuroprotective Agents, Maali Alshammari

Electronic Theses and Dissertations

Flavones are polyphenol natural products that are known to have neuroprotective effects against many diseases caused by the formation of reactive species. Flavonoids are subgroup of flavones and they are believed to function as antioxidants. Specifically, they target free radicals and eliminate its harmful effect on the cell. Fluoroflavones were designed to improve the potency of the antioxidant activity and potentially be used as neuroprotective agents. A monofluorinated and trifluoromethylated flavone were synthesized by using commercially available fluorination reagents, N-fluorobenzenesulfonimide; and Togni’s or Umemoto's respectively. After the synthesis of the desired flavones and their monofluorinated and trifluoromethylated derivatives, biological testing …

End Of Life Costs In Medicare Beneficiaries With Parkinson’S Disease, Sasikiran Nunna

Electronic Theses and Dissertations

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder which is characterized by motor and non-motor disorders. The prevalence of PD is high among elderly patients. Due to the chronic nature of PD, increasing prevalence and ageing population, it is important to understand the burden of PD at various stages of patient’s life so that value of PD therapies can be assessed. While direct healthcare costs during the life time of PD were assessed in previous studies, there is lack of information about end of life costs in PD patients. This dissertation aimed at filling the gap in literature …

Testing A Modified Model Of Stress Process For Understanding Quality Of Life Among Informal Caregivers And Assessing Their Formal Service Use, Nilesh V. Gangan

Electronic Theses and Dissertations

Informal caregivers provide timely care to family members who are disabled or have a chronic condition that requires close monitoring or constant assistance. To provide adequate support to informal caregivers there is a need to assess ways to improve their quality of life (QOL) and understand how formal services can be improved. This dissertation strives to extend the knowledge available for policy makers by examining the factors that can be targeted by policy makers to improve QOL of informal caregivers as well as the factors that enable the use of formal services provided to support informal caregivers. The psychometric properties …

Formulation Strategies To Address Physiological And Anatomical Constraints For Improved Topical Ocular Drug Delivery, Karthik Yadav Janga

Electronic Theses and Dissertations

Delivery of therapeutic molecules to the eye has been a complicated task owing to its anatomical and physiological barriers. This dissertation delineates several formulation strategies to circumvent dynamic and static constraints hampering the ocular drug delivery. Advanced vesicular systems, bilosomes and transfersomes, were prepared to improve the ocular pharmacotherapy of natamycin (NT). NT bilosomes and transfersomes were further loaded into in situ gel systems which transformed immediately to hydrogel, in the simulated tear fluid, with good viscoelastic and mucoadhesive properties.In vitro corneal transport studies confirmed the superior permeability characteristics of NT from the optimized bilosome and transfersome in situ gel …

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).

Development Of Continuous Manufacturing Process Of Acyclovir Ointment Using Hot-Melt Extrusion, Rui Wang

Electronic Theses and Dissertations

Hot-melt extrusion is a viable technology in preparing the pharmaceutical delivery system and has been considered as an attractive alternative to conventional processing methods. The objective of this study was to utilize the advantage of continuous manufacturing in HME to design and evaluate a formulation of topical semisolid ointment. Melt fusion ointments containing 5% of acyclovir (ACV) in water-soluble base with PEG 400, PEG 1500, and PEG 3350 polymers at various ratio were prepared. A design of experiment using I-optimal design was conducted. This design was used to study the influence of polymer ratio on the physicochemical properties of the …

Cheminformatic Approach For Deconvolution Of Active Compounds In A Complex Mixture - Phytoserms In Licorice, Manal Mohammad Alhusban

Electronic Theses and Dissertations

ABSTRACT After the validation of our in silico models by using the previous knowledge in this area the alerting phytochemicals from two Glycyrrhiza species (G. glabra and G. uralensis) were clustered. Exhaustive computational mining of licorice metabolome against selected endocrinal and metabolic targets led to the discovery of a unique class of compounds which belong to the dihydrostilbenoids (DHS) class appended with prenyl groups at various positions. To the best of our knowledge this interesting group of compounds has not been studied for their estrogenic activities or PXR activation. In addition some of the bis-prenylated DHS have been reported to …

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 …

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 …

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 …

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 …

Characterization Of Drug-Loaded Milled Extrudate Particles Produced By Hot Melt Extrusion Technology For Dry Powder Inhalers, Ahmed Almotairy

Electronic Theses and Dissertations

The aim of the current investigation is to develop a sustained-release dry powder inhalation (DPI) formulation through continuous Hot Melt Extrusion (HME) process and see the impact of Sodium Bicarbonate (SB) and Mannitol (MAN) on the hydrophobic Eudragit RL PO (ERLPO) polymer. Ball milling and air-jet milling were utilized to have powder with a particle size range that is required for inhalation. Air-jet milled formulations shopromising particle size results compared to ball milled formulations. All solid-state characterization studies revealed no change on Theophylline (TH) crystallinity or occurrence of drug-excipient interactions in physical mixtures and formulations. X2 formulation released TH constantly …

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.

Design Of Thermosensitive Hydrogel For Extended-Release Of Praziquantel, Sheng Feng

Electronic Theses and Dissertations

Parasitic diseases are a severe threat to people and animals. Praziquantel is the most comanti-parasitic drug with high efficiency, and it has been used to treat parasitic diseases for many years. However, it has very strong gastrointestinal and liver metabolism that leads to a strong first-pass effect and a short half-life. Additionally, the frequent oral administration was inconvenient for the large livestock. To overcome these drawbacks, this study aimed to develop an extended-release thermosensitive hydrogel formulation that was applicable to the injectable administration. The praziquantel-loaded hydrogel formulation based on poloxamer 407 (20%, w/v) was prepared, and two strategies for modifications …

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 …