Pharmacy and Pharmaceutical Sciences Commons^™

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 …

Unraveling Anticancer Activity And Pharmacokinetics Of Dihydroartemisinin Dimer Oxime, Lu Dai

Electronic Theses and Dissertations

Artemisinin is currently used as an antimalaria drug. Studies have shown its monomeric form exhibited promising anticancer effects by inhibiting the proliferation, inducing apoptosis, and increasing oxidative stress of tumor cells. Recently, several dimeric forms of artemisinin have been synthesized with more potent anticancer activity. In this study, nine dihydroartemisinin dimers with diversely functionalized linkers exhibited similar cytotoxicity against human breast adenocarcinoma MDA-MB-231 in vitro. Among these nine DHA dimers, DHA dimer oxime was selected for further anticancer activity and pharmacokinetic study. Our preliminary study shothat DHA dimer oxime displayed more than a 10-fold increase of antiproliferation effect over its …

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 …

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.

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 …

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 …

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 …

Evaluating Ways To Reduce Errors In Medication Reconciliations Performed By Nurses In A Rural Hospital Setting, Kalen T. Freeman

MPA/MPP/MPFM Capstone Projects

Medication reconciliation, also known as “med recs”, are an important part of a patient’s care during their hospitalization. A med rec is when hospital personnel generate a list of the medications the patient takes at home. Med recs are vital in the hospital admission process because home medications need to be restarted at appropriate times to fully care for the patient. Also, mistakes in a home medication list can lead to serious consequences in the patient’s health. This study focuses on med recs being performed at Marcum and Wallace Hospital in Irvine, Kentucky. More specifically, the study explores the different …

Impact Of Area-Under-The-Curve Monitoring For Vancomycin On Incidence Of Acute Kidney Injury In Orthopedic Patients, Kelli R. Keats

MPA/MPP/MPFM Capstone Projects

Vancomycin is an antibiotic used regularly in hospitals across the world. The most concerning adverse effect of vancomycin is its documented effect on kidney function. This study examines the impact of two dosing strategies of vancomycin on patients’ kidney function at the University of Kentucky Albert B. Chandler Medical Center. It specifically focuses on patients on the orthopedic service because these patients traditionally receive higher doses of vancomycin for longer periods of time due to the severity of their infections, which puts them at an increased risk of vancomycin-induced nephrotoxicity compared to other patients.

This study will serve as a …

Platelet Biology And Thrombosis: Juul E-Cigarette Exposure And 5ht2a Receptor Drug Discovery, Jean Emmanuel Montes Ramirez

Open Access Theses & Dissertations

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Development Of Ligand-Kinase Binding Affinity Predictive Model, Govinda Kc

Open Access Theses & Dissertations

Prediction of interaction between drugs or drug like compounds and targets, is of high importance in drug discovery process as it provides important insights into therapeutic potential and possible adverse effects. As the experimental testing would be highly expensive, laborious and time consuming, screening the molecules computationally before performing experiments would be cost effective, faster and convenient as a method of approach. In this study, I have developed computational models, leveraging machine learning techniques, to predict drug-kinase binding affinities. The predictive model is mainly built using the Random Forest (RF) machine learning method. This study is focused on kinases because …

Xflow: An Algorithm For Extracting Ion Chromatograms, Mathew M. Gutierrez, Rob Smith

Graduate Student Theses, Dissertations, & Professional Papers

Abstract: Mass spectrometry is a fundamental tool for modern proteomics. The increasing availability of mass spectrometry data paired with the increasing sensitivity and fidelity of the instruments necessitates new and more potent analytical methods. To that end, we have created and present XFlow, a feature detection algorithm for extracting ion chromatograms from MS1 LC-MS data. XFlow is a parameter-free procedurally agnostic feature detection algorithm that utilizes the latent properties of ion chromatograms to resolve them from the surrounding noise present in MS1 data. XFlow is designed to function on either profile or centroided data across different resolutions and instruments. This …

Role Of Glial Glutamate Transporter In Animal Model Of Acute And Chronic Inflammatory Pain, Ghallab Alotaibi

Electronic Theses and Dissertations

No abstract provided.

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 …

Formulation Development Of Natamycin Loaded Nanoemulsion For Ocular Drug Delivery, Kanika Goel

Electronic Theses and Dissertations

Natamycin (NT), also known as Pimaricin, is predominantly used as an anti-fungal medication for the treatment of fungal infections around the eye. The goal of the present study was to formulate and optimize NT loaded nanoemulsion (NT-NE) and examine its potential application in ophthalmic drug delivery. Placebos were evaluated with respect to particle size, PDI and ZP to identify the aqueous phase and lipid phase concentrations to be carried forward with NT-NE development. NT-NE were prepared by hot homogenization and ultra-probe sonication method, using Castor oil (CO) and Miglyol 812 as liquid lipids, Tween®80 and Poloxomer 188 as surfactants. NT-NE …

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 …

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 …

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 …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …