Pharmaceutics and Drug Design Commons^™

Quality Improvement (Qi) Project Aimed At Reducing Unnecessary Antibiotic Usage Among Older Adult Patients By Addressing Inappropriate Antibiotic Prescribing In Primary And Long-Term Care Settings, Pamela M. Thomas

Seton Hall University Dissertations and Theses (ETDs)

Antibiotic overuse among older adults remains a significant patient safety and public health concern. Recent national data indicate that approximately 30%–50% of outpatient antibiotic prescriptions may be unnecessary, particularly for viral or self-limiting conditions (Chua et al., 2021). Antimicrobial resistance has been associated with more than 1.27 million deaths globally (Murray et al., 2022). This quality improvement project evaluated a multifaceted antimicrobial stewardship intervention in primary and long-term care settings. Baseline review of 167 antibiotic cases revealed 37.1% were inappropriate or questionable, and 28.7% lacked adequate diagnostic documentation. The intervention incorporated provider education, electronic health record decision-support tools, audit and …

Ethical Decision-Making Frameworks In Ai-Driven Pharmaceutical Research & Development, Dhaval Dinesh Panchal, Osama Mohd Hash Ansari, Sudha Divya Madhuri Kallam

Harrisburg University Dissertations and Theses

Artificial intelligence is increasingly being utilized in pharmaceutical research and development to speed up drug discovery, enhance clinical trial design, and support regulatory decision-making. However, the increasingly rapid adoption of AI in the pharma industry has outpaced the development of consistent ethical governance, raising concerns related to data privacy, transparency, regulatory compliance, and stakeholder trust. This study explored the methods by which project managers could develop and utilize ethical decision-making frameworks to facilitate responsible AI implementation in pharmaceutical research and development. Guided by the Responsible Innovation framework, this research employed a mixed-methods design combining semi-structured interviews and quantitative surveys with …

Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods

Dissertations, Theses, and Capstone Projects

Allostery is a pervasive regulatory principle throughout biology, yet the structural pathways by which distal inputs alter active‑site chemistry within protein structures remain incompletely defined and exploited. This dissertation uses protein tyrosine phosphatase 1B (PTP1B) as a tractable model to map those pathways with complementary experimental and computational tools. I integrate high‑resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), room-temperature crystallography, NMR, steady-state kinetics, crystallographic pseudo-ensembles, and machine-learning-guided ligand discovery. The working premise is that regulation reflects redistribution within a conformational ensemble rather than a binary switch. That orthogonal perturbations by small molecules, mutations, and protein partners can be used to both …

Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao

Pharmaceutical Sciences (PhD) Dissertations

A significant problem faced in oncology is the lack of chemotherapeutic agents that are tumor site-specific, resulting in reduced therapeutic efficacy and unintended infliction of harm to surrounding healthy tissues and cells that often lead to serious side effects. Current strategies being explored to circumvent this issue aim to refine delivery of  chemotherapeutic agents specifically to tumor sites, which may be achieved via conjugation of these agents to biomarker-specific ligands. This forms the foundation of ligand-targeted drug delivery. Among different breast cancers, treatment of the triple-negative breast cancer (TNBC) subtype has been particularly challenging, largely due to the absence of …

Evaluation Of The Physical Properties And In Vitro Safety Of Chitosan-Quercus Infectoria Topical Gel, Rani Naga Rakshitha Tillapudi

Theses, Dissertations and Capstones

Due to ongoing inflammation, inadequate blood flow, oxidative stress, and reduced tissue regeneration, chronic diabetic wounds heal slowly, which is a serious health concern. It is important to examine novel strategies that tackle these issues because conventional treatments frequently fail. Therefore, this study examined the physical properties and biocompatibility of a novel topical gel formulated with chitosan and Quercus infectoria gall extract.

Over 28 days, pH, spreadability, texture, homogeneity, color, and drug concentration were assessed. UV-visible spectrophotometry and FTIR analysis were used to establish chemical stability. The MTT assay was used to test its safety in human dermal fibroblast adult …

Nanocomposite Mediated Delivery Of 5-Fluorouracil Using Silver Nanoparticles To Promote Wound Healing, Kamal Nath Kasi

Theses, Dissertations and Capstones

Chronic wounds, particularly in diabetic patients, remain a significant clinical challenge due to the complex interaction of persistent infection, chronic inflammation, and impaired cellular regeneration. Conventional drug therapies often fail to achieve effective treatment due to rapid drug degradation, poor targeting, and localized toxicity. This study explores a nanotechnology-based approach by developing and evaluating 5-FU loaded AgNP (AgNP–5FU) as a controlled drug delivery system. AgNP (AgNP) were synthesized and characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis, particle size, and zeta potential analysis, while Fourier Transform Infrared Spectroscopy (FTIR) analysis suggested possible interaction between 5-FU and the …

Development And In Vitro Characterization Of 5-Fluorouracil–Loaded Plga Nanoparticles For Controlled Drug Delivery, Kavya Yandapalli

Theses, Dissertations and Capstones

Non-Alcoholic Fatty Liver Disease (NAFLD) is a progressive metabolic disorder characterized by excessive lipid accumulation in hepatocytes and chronic inflammation. Nanoparticle-based drug delivery systems offer a promising strategy to enhance therapeutic efficacy while minimizing systemic toxicity. The objective of this study is to formulate and characterize 5-FU–loaded PLGA nanoparticles and evaluate their in vitro performance. 5-FU–loaded PLGA nanoparticles were prepared using the double emulsion solvent evaporation method. The nanoparticles were characterized by particle size, polydispersity index, zeta potential and SEM. Drug encapsulation efficiency, loading capacity and in vitro drug release studies were conducted. The formulated nanoparticles exhibited sizes within the …

Blister Packaging Versus Bottles: Caregiver Accuracy And Child Safety In Pediatric Medication Gummy Administration, Paolo Olimpiada

Nursing | Senior Theses

The safety of medication in pediatric settings has become an increasing concern as gummy-formulated medications have gained popularity in children’s care. Gummy-formulated medications have a close resemblance to candy, and this may mislead children to ingest additional doses or more than what was prescribed. Children also depend a lot on their caregivers for medications. Therefore, the design of packaging would be impactful in supporting medication dosing accuracy. And studies have evaluated safety features of packaging related to adherence, misuse, and unintended administration. However, limited studies have examined the influence of medication packaging on the dosing accuracy at the time of …

Local Lung Delivery Of Ginkgetin For Therapeutic Intervention In Lung Fibrosis, Cimone L. Richardson

Theses and Dissertations

Lung fibrosis (LF) is a progressive, irreversible pathological condition in the lungs that is ultimately fatal. Current drug treatments (nintedanib, pirfenidone, and nerandomilast) slow disease progression but cause significant systemic adverse effects due to oral administration. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, may play a role in LF progression and represent a novel anti-LF target. Ginkgetin (GKT), a natural biflavonoid, is a potent TRPV4 inhibitor with anti-inflammatory and antioxidative properties. Local lung delivery could achieve high local lung concentrations while minimizing systemic exposure. Accordingly, this project evaluates GKT's therapeutic intervention efficacy in LF via local lung …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …

Investigating The Immunostimulatory Potential Of Dsrna-Silk Nanoparticle Complexes In Melanoma, Samuel J. Peters

Theses and Dissertations (Comprehensive)

The rate of resistance to immune checkpoint inhibitor treatment in metastatic melanoma is quite high, with an overall rate of 70%. Melanoma achieves these high rates of resistance by suppressing the immune response in the tumour microenvironment (TME), making them immunologically “cold”. The type 1 interferon response could be leveraged to initiate immune responses in melanoma, making their “cold” TMEs “warm” again. Double-stranded ribonucleic acids (dsRNAs) are potent activators of an innate immune response; however, they are susceptible to degradation by nucleases present in the body and need a carrier. Silk nanoparticles (SNPs) are an ideal drug-delivery platform as they …

Development Of Self-Assembled Polymeric Polyplexes For Microrna Delivery: Toward Treatment Of Alcohol-Associated Liver Disease, Marjina Akter Kalpana

Theses & Dissertations

Self-assembled polymeric polyplexes have the potential to serve as an RNA interference (RNAi) delivery platform for the combined inhibition of CXCR4 and miR-155 in the treatment of alcohol-associated liver disease (AALD). A central challenge in RNA delivery is balancing the extracellular stability of polyplexes, cellular uptake, and intracellular release of RNA cargo. We developed polymeric polyplexes using the CXCR4-antagonist polymer PAMD, designed to target CXCR4 on activated hepatic stellate cells (HSCs) and deliver therapeutic miRNA to activated Kupffer cells (KCs) in fibrotic liver. We improved the polyplexes by cholesterol modification of PAMD and by PEGylation of PAMD-Ch. The cholesterol modification …

Development And Characterization Of Non-Viral Delivery Systems For Pulmonary Delivery Of Nucleic Acid Therapeutics, Kasturi Siddhanta

Theses & Dissertations

The development of non-viral delivery systems for pulmonary delivery of nucleic acid therapeutics is driven by the need for safer and more accessible approaches to treat lung diseases, while avoiding the systemic side effects and immune responses associated with viral vectors. Such systems encompass both non-invasive inhalation-based platforms, and systemically administered platforms designed to achieve localized lung delivery. These strategies aim to enable high drug concentrations at the site of action, rapid onset of therapeutic effect, and greater therapeutic efficacy than existing treatments. Designing effective pulmonary delivery systems requires precise optimization of particle properties—including size, morphology, surface characteristics, cell-specific targeting, …

Breastfeeding Safety Following Maternal Anesthesia: A Guideline Development, Megan Honea, Mary Johnson

Doctoral Projects

Recommendations regarding breastfeeding following maternal anesthesia are inconsistent and often not up to date with current best practice guidelines. Previous recommendations have led to mothers unnecessarily “pumping and dumping” breast milk has benefits for both mother and baby. These benefits include (a) increasing the infant’s access to colostrum, (b) encouraging mother-baby bonding, (c) improving the mother’s breastfeeding experience, (d) and providing significant health benefits to the infant. The purpose of this scholarly project was to develop a set of evidence-based recommendations that focus on mothers who desire to breastfeed following general anesthesia. These recommendations will highlight maternal- fetal transfer of …

Avaren-Fc's Effects On Lymphoma Cells., Jacob Hahn

Electronic Theses and Dissertations

This thesis investigates the therapeutic potential of Avaren-Fc (AvFc), a novel lectin fusion protein that integrates the Fc region of human IgG1 with the engineered lectin Avaren, specifically targeting lymphoma. The study delineates the in vitro binding capabilities of Avaren-Fc with a human B-cell lymphoma cell line, a canine B-cell lymphoma cell line, healthy canine peripheral blood mononuclear cells (PBMCs), and healthy human PBMCs. AvFc was shown to exhibit significant binding to human lymphoma cells. Furthermore, the direct cytotoxicity of Avaren-Fc against canine lymphoma cells, canine lymphoma cells and healthy canine PBMCs was assessed. It was found that there is …

Safety Evaluation Of Epicertin, An Oral Biotherapeutic Candidate For Treating Ulcerative Colitis: A 28-Day Repeated Dose Toxicity Study., Jimmy Fernando Cifuentes Jimenez

Electronic Theses and Dissertations

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic, relapsing inflammation of the colon and rectum with limited treatment options. Among them, immunosuppressive agents have a high rate of adverse side effects and do not cure the disease. EPICERTIN (EPT), a recombinant variant of the cholera toxin B subunit (CTB) with a C-terminal hexapeptide extension consisting of a KDEL endoplasmic reticulum (ER) retention motif, is a promising oral biotherapeutic candidate for the treatment of UC. EPT has demonstrated mucosal healing activity in mouse models of colitis and human colonic explants. EPT's mechanism of action involves binding to GM1 …

Cbl Regulation Of C-Met Signaling In Corneal Epithelial Cells., Kate Elise Tarvestad Laise

Electronic Theses and Dissertations

The cornea is the most anterior portion of the eye and permits light passage through to retina, allowing formation of a clear image as long as it remains healthy. If the cornea sustains damage, it creates and entrance for foreign body invasion, infection, and ultimately blindness in the immunocompromised eye. Healing the corneal tissue is critical for vision restoration and pain alleviation, as it is the most densely innervated tissue in the body. Growth factors and their cognate receptors are currently under investigation as tools to restore proper corneal physiology. We hypothesize that manipulating the hepatocyte growth factor (HGF) /c-Met …

Lipid Nanoparticle-Mediated Drug Delivery To Cns Targets, Purva Khare

Electronic Theses and Dissertations

Lipid nanoparticles (LNPs) have revolutionized drug delivery, particularly in the delivery of gene silencing siRNA to the liver (Onpattro) and COVID-19 mRNA vaccines (Pfizer-BioNTech, Moderna). It is no exaggeration to state that the LNP delivery technology has protected billions of vaccinated people against a severe COVID-19 infection and subsequent mortality. Despite extensive research on LNPs for hepatic and muscle delivery, their potential for brain drug delivery remains underexplored. Many neurological disorders lack effective treatments, making LNP-based approaches promising for crossing or targeting drug delivery to the blood-brain barrier (BBB). Brain endothelial cells (BECs), a key component of the BBB, play …

Engineering Cxcr2-Ligand-Based Fusion Proteins To Modulate Myeloid Cell Trafficking In Pancreatic Cancer, Benjamin N. Christopher

MUSC Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers, and limited treatment options exist. Immunotherapy is effective in some cancer types, but the immunosuppressive tumor microenvironment (TME) of PDAC is a barrier to effective immunotherapy. CXCR2+ myeloid-derived suppressor cells (MDSCs) are abundant in PDAC tumors in humans and in mouse models. MDSCs suppress effector cell function, making them attractive targets for restoring anti-tumor immunity. The studies outlined in this dissertation (1) link tumor-intrinsic oncogenic signaling to dysregulated myeloid activity in PDAC, (2) describe a rationally designed fusion protein and potent inhibitor of CXCR2+ myeloid …

Investigating The Cytotoxic Effects Of Amino Acid-Based Ionic Liquids And Peg-Pla Nanoparticles On Mcf10a Human Breast Epithelial Cells For Drug Delivery Applications, Ella C. Mertins

Honors Theses

This study investigates the cytotoxic effects of polyethylene glycol-polylactic acid (PEG-PLA) nanoparticles (NPs) both bare and coated with choline-based ionic liquids (ILs) on MCF10A human breast epithelial cells. The goal was to evaluate how IL-modified NPs influence cell viability at varying concentrations and to assess their potential as drug delivery systems. Three choline-based ILs, Choline-L-Asparagine 1:1, Choline-DL-Isoleucinate 1:1, and Choline-L-Leucinate 1:1, were used as surface coatings for PEG-PLA NPs. Additionally, the ILs were tested independently to establish a baseline for their cytotoxicity. Using a luminescent ATP-based viability assay following the treatment of MCF10A cells, the ILs were found to be …

The Endocannabinoid System's Influence And Modulation Of Nociception, Doreen M. Flannery

Honors Thesis

The anatomy and physiology of pain is a well-defined pathway where noxious stimuli is processed by different systems in the brain. The central research question of this review is how can we better understand the neurobiological effects pain has, and assess if there is therapeutic potential in using endocannabinoids to modulate these effects. Endocannabinoids are signaling molecules that play a key role at both the cellular and molecular level in modulating both acute and chronic pain by influencing different processes within each level that affect how the body responds to both internal and external stimuli. The endocannabinoid system is a …

Studies To Understand The Stability And Liabilities Of Legumain-Cleavable Antibody-Drug Conjugates, Michele Yi

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) offer targeted drug delivery of potent cytotoxic payloads, minimizing systemic toxicity. However, the stability of the linker is integral to ensure that there is minimal off-target payload release and little systemic toxicity. This study analyzes the physical and biological stability of our new legumain-cleavable vs traditional cathepsin-cleavable antibody-drug conjugates (ADCs), with a focus on hydrophobicity, thermal stability, aggregation, and biological payload release. Our findings indicate that decreased hydrophobicity of the legumain-cleavable ADCs compared to cathepsin-cleavable ADCs is correlated with decreased aggregation (predicting lower uptake by liver macrophages and therefore slower clearance and less systemic toxicity) and lower …

The Design, Construction, And Testing Of Mrna Vaccine Against Equine Herpes Virus, Bhawana Devkota

LSU Master's Theses

Equine Herpesvirus-1 (EHV 1) is a worldwide significant pathogen that causes respiratory illness, abortion, and neurological disorders in equine. Current vaccines, including live attenuated, inactivated, and subunit platforms, do not prevent viral latency, mucosal shedding, or cross-strain immunity, requiring alternative approaches. To address these gaps, this project explores the design, synthesis, and in vitro testing of an mRNA vaccine targeting immunogenic EHV 1 glycoprotein (gB, gC, gD, gG, and gM). Epitopes were computationally predicted using the Immune Epitope Database (IEDB), codon-optimized for Bos taurus, and cloned into pUCIDT vectors using SP6/T7 promoters. In vitro transcription (IVT) used nucleotide modifications …

Evaluation Of Disulfiram And Derivatives As Antimicrobial Adjuvants, Surya Bhaskar Karuturi

Theses, Dissertations and Capstones

Disulfiram (Antabuse) is an oral drug used for the treatment of alcohol dependence. Previous studies showed that disulfiram has antibiotic activity on multidrug-resistant bacteria. Here disulfiram was further evaluated for its ability to increase the potency of existing antimicrobials against the bacteria and yeast by acting as a drug adjuvant. Microbial cultures were treated with antibiotic or antifungal drugs in combination with disulfiram and its derivatives to determine whether potency is increased. The structure activity relationship (SAR) of disulfiram analogs was assessed against a triazole resistant Aspergillus panel. It showed that the shorter chained analogs of disulfiram are more potent …

Rwanda's Natural Remedies: A Fresh Look At The Fight Against Malaria, Leandre Nsabimana Ndisanze

Pomona Senior Theses

Malaria remains one of the most devastating parasitic diseases globally, disproportionately affecting sub-Saharan Africa, where Rwanda continues to face high transmission rates and rising resistance to conventional interventions. Despite decades of control efforts, the emergence of drug-resistant Plasmodium falciparum and insecticide-resistant Anopheles mosquitoes threatens to reverse recent gains. This research responds to the urgent need for sustainable and culturally relevant alternatives by exploring the therapeutic potential of Rwandan traditional medicinal plants. These indigenous remedies, long used by local healers, offer an underexplored reservoir of bioactive compounds that may provide the basis for novel antimalarial drugs.

The central hypothesis of this …

Development Of Novel Carbohydrate-Based Nanoparticles For Precision Drug Delivery, Krystal Ann Hughes

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticle-based drug delivery has made tremendous advancements in the last decade. However, several critical factors, including precision drug delivery at the site of interest, long-term storage stability, and controlling release profiles of drugs in the systemic circulation, need to be addressed for successful clinical translation of nanomedicine. This dissertation presents novel carbohydrate-based nanoparticles that achieve precise intracellular delivery and therapeutic release at the disease site. We present the formulation and optimization of polymeric and polymer-lipid hybrid nanoparticles that enable precision intracellular delivery and passive accumulation of therapeutics in the bone marrow. Intracellular delivery is highly impactful and sought after. One …

High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy, Janapriya Vijayakumar

Honors Undergraduate Theses

Current therapy for arthritis predominantly focuses on the symptoms rather than the underlying causes of disease progression. Thus, it is necessary to identify novel drugs which target the underlying molecular basis of such diseases. Using high-throughput cell-based drug screening, we screened 458 different compounds, narrowed down from 811 starting compounds from the NIH Mechanistic Set. We selected drugs from the Mechanistic Set following Lipinski's Rule of 5 to ensure optimal pharmacokinetic properties. The study used modified primary human chondrocytes (IIAM-PRG4Luc), which secrete a lubricin promoter-driven luciferase reporter. We use this luciferase expression as a proxy to measure lubricin, a compound …

Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug, Swathi S. Menon

Honors Undergraduate Theses

Osteoarthritis (OA) is a degenerative disease that affects many people worldwide. Current methods of treatment are palliative, and no treatment exists to fully reverse or cure OA once it begins to progress. The discovery of a disease-modifying osteoarthritic drug (DMOAD) would increase the quality of life for millions and reduce the need for invasive procedures. Screening FDA-approved drugs ensures more promise due to their known safety profile and potential for faster translation to the clinic. The goal of this project was to conduct dose-response assays with FDA-approved drugs that have been shown to stimulate lubricin production in cells that mimic …

Optimization Of Chitosan Nanoemulsion And Its Application In Delivering 5-Fluorouracil And Quercus Infectoria For Wound Healing, Kalkedan Ameha

Theses, Dissertations and Capstones

BACKGROUND: Chitosan-based nanoemulsions are increasingly recognized for their potential in enhancing drug delivery for wound healing applications. The integration of Quercus infectoria (Qi) extract, known for its antibacterial and anti-inflammatory effects, with 5- fluorouracil (5-FU), a chemotherapeutic agent that regulates abnormal cell proliferation, presents a synergistic approach for treating chronic and non-healing wounds. Ensuring long-term physicochemical stability of these nanoemulsions is critical for their therapeutic viability.

OBJECTIVE: To optimize and characterize a chitosan-based nanoemulsion for the codelivery of 5-FU and Quercus infectoria extract, with emphasis on physicochemical properties including particle size, polydispersity index (PDI), and zeta potential. The …