Pharmaceutics and Drug Design Commons^™

Effects Of Glucagon And Insulin On Sw480 Colorectal Cancer Cells In Combination With Cisplatin, Sarah M. Gabous, Andrea Florian

SPARK Symposium Presentations

Colorectal cancer is known to be one of the most common forms of cancer in the world. Over time, treatment responses are affected by various metabolic changes along with chemotherapies. Glucagon signaling and Insulin are linked to colorectal cancer and have also been shown to affect tumor growth, as well as the chemotherapy drug response.In this experimental study, the purpose was to determine whether glucagon and insulin decrease the viability of SW480 colorectal cancer cells during cisplatin (CDDP) treatment. CRC cells were treated with cisplatin alone and in combination with either glucagon or insulin, and cell viability was measured to …

Off-Label Uses Of Deucravacitinib For Inflammatory Skin Conditions: Cases And Literature Review, Alexandra Nigro, Isabel C. Silva, Benjamin Gerstein, Jasper Dayanan, Saakshi Khattri

Department Dermatology Faculty Publications

Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Deucravacitinib may offer a more selective approach compared to traditional Janus kinase (JAK) inhibitors. Emerging data support the use of deucravacitinib in inflammatory dermatoses beyond psoriatic disease. We present our clinical experience using deucravacitinib off-label in patients with challenging inflammatory skin disease and contextualize our findings within the current literature. We report three female patients aged 31–63 years with refractory inflammatory skin conditions, including two with dermatomyositis and one with pityriasis rubra pilaris (PRP). All patients had persistent …

A Systematic Review On Niosomes: Composition, Preparation, And Applications, Sanket Gawade Mr., Sunil Attimarad, Vishakha Desai Ms.

Manipal Journal of Medical Sciences

Conventional drug carrier systems are restricted owing to poor bioavailability, weak stability and non-specific localization, which causes systemic toxicities and reduced therapeutic efficacy. Niosomes, one of the nonionic surfactant vesicular systems, have been suggested that value to overcome these constraints. In this review, we give an account of recent progress in niosome research, highlighting their merits, composition, characterization, and applications.

Niosomes offer several advantages including increased drug bioavailability, targeted delivery and reduced toxicity. Bilayered niosomes can entrap both hydrophilic and lipophilic drugs, therefore allowing simultaneous delivery of actives components. We provide an overview of various techniques for niosome preparation including …

Longitudinal Patterns Of Urinary Biomarkers Of Placental And Renal Function In Pregnancy And Associations With Early Pregnancy Exposure To Phthalates And Replacements, Erin E. Mcnell, Danielle R. Stevens, Barrett M. Welch, Suzanne Fenton, Antonia M. Calafat, Julianne Cook Botelho, Elena Sinkovskaya, Ann Przybylska, George Saade, Alfred Abuhamad, Kelly K. Ferguson

Department of Obstetrics & Gynecology Faculty Publications

Phthalates and replacements are endocrine-disrupting chemicals that may interfere with early pregnancy processes such as placentation and renal adaptation. Placental and renal biomarkers may help examine these toxicologic mechanisms. This study aims to characterize longitudinal changes in urinary protein biomarkers of placental angiogenesis (sFlt-1, PlGF, sEng) and renal function (KIM-1, NGAL, nephrin), and investigate associations with early pregnancy exposure to phthalates and replacements. Among 291 participants from the Human Placenta and Phthalates prospective cohort, urinary metabolites of eight phthalates and two replacements were quantified at up to 2 time points from 12 to 15 weeks gestation. Repeated measures were averaged …

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 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 …

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 …

Self-Assembly Of Anti-Inflammatory Peptide Amphiphiles For Mucosal Health, Maria José Gómara, Ignacio Pérez-Pomeda, Ramon Pons, Paul Ziprin, Carolina Herrera, Isabel Haro

CONRAD Publications

Broad spectrum anti-inflammatory peptide amphiphiles (AIF-PAs) have been developed as an innovative strategy for the treatment of chronic mucosal inflammation and the prevention of HIV transmission. Novel lipopeptides based on two linear sequences of anti-inflammatory peptides were obtained by solid-phase peptide chemistry. In a pilot study, ex vivo exposure of colorectal tissue explants from Crohn's disease patients to AIF-PAs induced a downregulation of the proinflammatory profile. Furthermore, the HIV inhibitory potency of AIF-PAs was evaluated ex vivo in colorectal tissue explants, obtaining sub-micromolar IC₅₀ values. Characterization of AIF-PAs self-aggregation in aqueous solution revealed that the net charge distribution within the …

Depemokimab: A Twice Yearly Anti-Il 5 Biologic For Chronic Rhinosinusitis With Nasal Polyps (Crswnp) - A Narrative Review, Marn Joon Park, Joseph K. Han, Kent K. Lam

Department of Otolaryngology (ENT) Faculty Publications

Depemokimab is a monoclonal antibody that targets interleukin-5 with enhanced binding affinity and an extended terminal elimination half‑life of 6-8 weeks. The unique pharmacodynamic features of depemokimab enable sustained suppression of type 2 inflammation with twice‑yearly subcutaneous dosing. This narrative review provides details of depemokimab's molecular profile, pharmacokinetics, and pharmacodynamics and results regarding the clinical efficacy and safety of depemokimab from recently published Phase 3 clinical trials for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). In 528 severe adult CRSwNP patients (ANCHOR‑1/‑2 trials), depemokimab achieved Δ total endoscopic nasal polyp score by -0.70 (p <  .001) and Δ nasal obstruction verbal response scale by -0.24 (p = .003) at week 52, compared to placebo. Twice‑yearly 100 mg depemokimab provides durable eosinophil suppression and with a safety profile comparable to placebo in Phase 3 trials for CRSwNP. Future work should refine biomarkers and assess comparative cost‑effectiveness and long‑term adherence, safety, and effectiveness.

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 …

Hot-Melt Extrusion-Based Solid Dispersion Of Aripiprazole: Preparation, Characterization, And In Vitro Evaluation, Nensi Raytthatha, Jigar Ramanlal Vyas

The Thai Journal of Pharmaceutical Sciences

Background: Aripiprazole (ARI), a biopharmaceutics classification system (BCS) class IV drug, exhibits poor water solubility and low permeability, resulting in limited bioavailability. Addressing these challenges requires innovative approaches to enhance solubility. This study focuses on the development and evaluation of solid dispersions (SDs) of ARI using “hot-melt extrusion,” (HME) a scalable and solvent-free method known for its ability to create stable amorphous structures. Soluplus^® (SP) and Kollidon® 30 were employed as hydrophilic polymeric carriers to improve the solubility and stability of the amorphous drug form. Results: SDs were prepared by taking drugs and carriers (SP and Kollidon …

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, …

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 …

Abc Pharmaceutical Company Change Model: Implementing J.P. Kotter's 8-Step And Adkar Change Models For Ethical Alignment, Shelbi B. Chandler, Amalfi Gayosso, Alison Lawton, Ali Holness-Roland

The Scholarship Without Borders Journal

In this paper, we use the pseudonym ABC Pharmaceuticals (ABC) to refer to the company under examination, GlaxoSmithKline (GSK). ABC Pharmaceutical (ABC) must assess, adapt, and change to ensure regulatory compliance, maintain and attract employees, and remain competitive. ABC has a history of erroneous practices and is at risk internally with employees, and externally with regulators and the public sectors. The authors applied J.P. Kotter’s (1996) 8-step and the ADKAR (Hiatt, 2006) models for change management. J.P. Kotter’s top-down model addresses leadership’s role in creating a compelling vision aligned with its actions, and the ADKAR bottom-up model assesses employees’ readiness …

Selenium Nanoparticles As Versatile Delivery Tools, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Kyle Yep, Keykavous Parang

Pharmacy Faculty Articles and Research

Selenium nanoparticles (SeNPs) have emerged as promising metal-based nanoparticles for drug delivery due to their unique physicochemical properties, intrinsic bioactivity, and biocompatibility. SeNPs offer a lower toxicity, higher bioavailability, and flexibility to be customized for surface chemistry compared to traditional selenium compounds. Advances in synthetic strategies, including chemical reduction, green biosynthesis, and surface functionalization with polymers, peptides, or ligands, have improved their stability, targeting capability, and circulation time. SeNP-based systems have demonstrated unique anticancer, antimicrobial, and anti-inflammatory activities, as they can function as drug carriers and active therapeutic agents. The surface of SeNPs has been functionalized with ligands such as …

Assessment Of Stroke Priority Status On Door-To-Reversal Time And Outcomes In Anticoagulant Associated Intracranial Hemorrhage, Kayla Mitzel, Jonathan Kline, Thomas J. Wolfel, Erika Dittmar, Nina Cruz, Felipe De Los Rios La Rosa, Heidi Clarke

Nursing & Health Sciences Research Journal

Background: The emergent reversal of anticoagulation in the setting of intracranial hemorrhage (ICH) is critical, and it is essential that comprehensive stroke centers adhere to the American Heart Association (AHA) metrics for door-to-reversal within the designated 90 minutes. The objective of this review is to evaluate individuals classified as stroke alert priority 1 and non-stroke alert and compare AHA metrics for door-to-reversal times and clinical outcomes when diagnosed with ICH.

Methods: Single-center observational, retrospective review that compared stroke alert priority 1 individuals to non-stroke alert individuals who were diagnosed with an ICH and taking an anticoagulant prior to admission. The …

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 …

Development And Optimization Of Moxifloxacin Solid Lipid Nanoparticles Via Double Emulsion Organic Solvent Free Technique Applying Box–Behnken Experimental Design, Esraa M. Elshazly, Mona G. Arafa, Samia A. Nour

Pharmacy

The current research proposes the preparation of Moxifloxacin-loaded solid lipid nanoparticles through a solvent-free double emulsion technique, to overcome chronic wound healing limitation. The independent variables: stearic acid, Span 80, and Tween 80 were optimized via Box–Behnken design, based on entrapment efficiency (EE%), zeta potential (ZP), and particle size (PS). To statistically optimize the formulation variables, a three-factor, three-level (3³) design involving 15 runs was employed and optimization was carried out to attain maximum EE% and ZP and minimum PS yielding an overall desirability of 0.851. Results indicated that increasing stearic acid enhanced EE%, Span 80 increase PS, and Tween …

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 …