Pharmaceutics and Drug Design Commons^™

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 …

Application Of Bioactive Materials Primary Cilia As A Novel Delivery Vehicle, Ayan K. Barui, Farideh Amirrad, Vansh Goel, Sharareh Ohadi, Rajasekharreddy Pala, Ashraf M. Mohieldin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like structured cell organelles functioning as cellular antennae with chemosensory and mechanosensory roles. Dysfunction of cilia results in ciliopathies, including renovascular diseases (polycystic kidneys, hypertension, aneurysm), mental impedances (Alzheimer's disease, Parkinson's disease, dementia), metabolic diseases (obesity, developmental skeleton defects), blindness, and so on. With a diameter of 150 nm, cilia can be cleaved, released and circulated in the body as injury biomarkers. We here assessed the potential use of isolated cilia as a novel delivery vehicle. Cilia were isolated from renal epithelial cells, and a specific-targeting chemotherapeutic was designed on the cilia. The data show a remarkable …

Valproic Acid Loaded Niosomal In Situ Gel: A Novel Approach For Epilepsy Treatment, Rutuja Bastapure, Akshay Gawali, Gopal Lohiya, Kranti Satpute, Mahesh Birajdar, Sameep Sonvane

International Journal of Health and Allied Sciences

Valproic acid is an antiepileptic medication that is primarily used to treat epilepsy and bipolar disorder. This investigation was designed with three objectives in mind. First, improve the solubility and bioavailability of the BCS class II medicine valproic acid; second, make it easy to give the drug to an epileptic patient during an episode; and third, lower the dosage for long-term treatment. Niosomal formulations were optimized using various Tween and Span range ratios. The formulations were made using the ether injection method. The formulation's morphological characterization, entrapment efficiency, viscosity, and particle size were evaluated. Valproic acid niosomes prepared with Tween …

Development And Assessment Of Liposomal Nasal Spray For The Treatment Epilepsy, Sayali Dongare, Sushmaji Sontakke, Gopal Lohiya, Shoeb Syed, Rohit Sarda

International Journal of Health and Allied Sciences

Abstract:

Background: Levetiracetam is a pyrrolidine class antiepileptic drug mainly used to treat epilepsy and seizures.

Objective: The purpose of this research was to synthesize a liposomal nasal spray incorporating levetiracetam for nose to brain delivery in epilepsy.

Materials and methods: The preparation method employed thin film hydration to prepare liposomes loaded with levetiracetam with lecithin and tween 80 at different concentrations. The liposome formed were characterized in terms of particle size and entrapment efficiency. Finally, the prepared liposomes were converted into nasal spray and characterized for drug content, pH, viscosity, in vitro release profile, clarity, Ex-vivo permeation study. …

Fluorescent Labeling And Size-Dependent Uptake Of Mesoporous Silica Nanoparticles In Ovarian Cancer Tumor Spheroids, Kimberly R. Berardis

Honors Scholar Theses

Ovarian cancer is the most lethal gynecologic malignancy, with most patients presenting at an advanced stage. While surgical debulking improves survival, nonresectable tumors (<1 cm) contribute significantly to morbidity and remain difficult to treat. Nanocarrier-based drug delivery systems offer an innovative approach to targeted therapy and palliation. In vivo models have demonstrated that intraperitoneally delivered mesoporous silica nanoparticles (MSNs) preferentially accumulate in tumors with low systemic exposure, enabling targeted chemo- and radiotherapy.

MSNs are particularly suited for radiotherapeutic delivery, as their strong interactions with tumor extracellular matrices drive selective uptake. Additionally, they exhibit excellent stability under neutron flux, allowing for loading with stable isotopes and irradiation immediately prior to administration. High radionuclide retention after dilution further minimizes systemic exposure and toxicity.

A key …

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 …

Advancing A Patient- And Carer-Centered Approach For The Clinical Development Of New Therapeutics For Aneurysmal Subarachnoid Hemorrhage: Insights From A Qualitative Study, Sonya Abraham, Silvia Amaro, Ellyn Getz, Sylvia Herget, Gregory J. Kato

Journal of Patient-Centered Research and Reviews

Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by a high rate of fatality and high risk of secondary brain injury. More treatment options are needed to improve outcomes. There are very few reports in the medical literature involving patient experience of aSAH, which is known for its unexpected onset and profound medical impact. Improved understanding of this patient experience would help make future clinical research more patient centered. To this end, we convened an advisory board consisting of aSAH patients and care partners in the United States. Participants emphasized the critical role that care partners play during hospitalization and in accessing …

Hexasodium Fytate (Snf472 Or Csl525) Inhibits Ectopic Calcification In Various Pseudoxanthoma Elasticum And Calcinosis Cutis Animal Models, Miguel Ferrer, Maria Pérez-Ferrer, Marc Blasco, Ida Jacobs, Qiaoli Li, Olivier Vanakker, Lisa Dangreau, Andrea López, Gianluca Malagraba, Firas Bassissi, Joan Perelló, Carolina Salcedo

Department of Biochemistry and Molecular Biology Faculty Papers

Background/Objectives: Ectopic calcification is a pathological condition characterized by the mineralization of soft tissues due to the deposition of calcium phosphate crystals. Hexasodium fytate (CSL525, previously known as SNF472) is a crystallization inhibitor being developed for the treatment of ectopic calcification-related disorders. Our aim was to investigate CSL525 for the treatment of soft-tissue calcification disorders in animal models of pseudoxanthoma elasticum and calcinosis cutis. Methods: In a first study, abcc6^-/- zebrafish larvae were exposed to 1 mM CSL525 for 7 days or kept under the same conditions without CSL525, and spinal mineralization was quantified. In a second study, abcc6 …

Preparation And Evaluation Of Mesoporous Celecoxib For Improved Antiarthritic Activity In Rodents, Reena I. Fernandaes, Sayani Bhattacharyya

The Thai Journal of Pharmaceutical Sciences

Background: Celecoxib, a model anti-inflammatory drug, used in the management of arthritis exhibits limited oral bioavailability and slow onset of action due to its poor solubility. Objective: The present study explores a mesoporous drug delivery of celecoxib to investigate the efficacy of its antiarthritic activity in animal models, and develops a low-oral dose therapy. Materials and Methods: The solvent evaporation method was employed for the preparation of mesoporous delivery of celecoxib, using Syloid^®, and Neusilin^®, at a molar ratio of silica/ drug 1:2.5. The formulations were characterized for drug loading, in vitro drug release, and material …

Enhancing Topical Drug Delivery Of Apremilast Through Niosomal Gel Formulation: Ex Vivo Skin Permeation And In Vivo Evaluation For Psoriasis, Megha Shyam Matlapudi, Anka Rao Areti, Yukti Jaiswal, Veeresh Bantal, Raghavender Medishetti

The Thai Journal of Pharmaceutical Sciences

Background: Psoriasis is a dynamic and chronic disease characterized by inflammatory changes and an increased rate of keratinocyte proliferation leading to the formation of erythematous scleroderma plaques with a silvery sheen. The existing therapies come with shortcomings in terms of effectiveness and leave behind a trail of side effects. Hence, there is a need of alternative therapeutic measures. Objectives: This study aimed to assess the therapeutic potential of Apremilast Niosomal Gel (APR Nio Gel) in treating psoriasis, comparing its effectiveness with conventional gel (APR Gel) and oral suspension (APR Oral) formulations. Materials and Methods: Apremilast niosomes were prepared by thin …

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 …

Takotsubo Cardiomyopathy: A Case Of The Broken Heart, Lilian Huynh, Kaylee Putney

Annual Research Symposium

Takotsubo cardiomyopathy (TC), or "broken heart syndrome," is a rare cardiac condition causing temporary left ventricular dysfunction due to severe stress. Though the exact cause is unclear, it mimics myocardial infarction and can lead to cardiogenic shock. Current treatment lacks specific guidelines and relies on heart failure protocols. We report a case of a patient with TC-induced cardiogenic shock, likely triggered by emotional stress. She required vasopressors, a percutaneous intervention, an Impella device, and guideline-directed medication therapies. This case underscores the significance of establishing guideline optimizations for managing TC and cardiogenic shock.

In-Silico Modeling And Characterization Of Kcc2 Protein Interaction With A Small Molecule Direct Agonist Identifies Potential Binding Sites For Modulating Behaviors Associated With Substances Of Abuse, William Hai Dang Ho, Alfred Amendolara, Kenyon Mitchell, Jaden Miner, Ruth Northcott, Braxton Bingham, Andrew J. Payne

Annual Research Symposium

Purpose

KCC2 is a potassium-chloride cotransporter that plays a critical role in neuronal function by regulating GABAergic signaling via chloride gradients. Maintaining this concentration gradient is crucial for balancing excitation and inhibition in the brain. While KCC2 dysregulation has been implicated in epilepsy and seizures, recent studies suggest that KCC2 inhibition results in phenotypes mirroring those seen in chronic opioid dependence. As such, increasing evidence support KCC2 being a potential therapeutic target for modulating behaviors associated with substances of abuse. Currently, only a few direct small molecule agonists against KCC2 have been reported, and no definitive active site on the …

Centella Asiatica: Recent Cosmeceutical Uses For Treatment Of Skin Diseases, Iman I. Soliman, Nouran Medhat, Huda Saleh, Mai El Halawany

Bulletin of Faculty of Pharmacy Cairo University

Centella asiatica is one of the well-known herbal species used in traditional medicine across Asia such as India, Indonesia, and China. It had been used as a medicinal plant for hundreds of years. Besides its general pharmacological activities such as neuroprotection, anti-cancer and anti-diabetes. It demonstrated effective dermatological actions as being a potent anti-inflammatory, antioxidant, healing and moisturizing properties. The major constituents responsible for these effects were triterpenoids. Triterpenoids included asciaticoside which was reported to induce collagen synthesis. Madecassoside was known for its wound healing properties. It was well known for its efficiency in improving the treatment of hypertrophic wounds. …

Orchestrating Cytosolic Access: The Partnership Of Cationic Lytic Peptide L17e And Potassium Channel Kca3.1, Keykavous Parang

Pharmacy Faculty Articles and Research

In this issue of Molecular Therapy, the study by Kuriyama et al.¹ represents an advance in the field of intracellular delivery systems by elucidating a novel mechanism for cytosolic delivery mediated by a cationic amphiphilic lytic peptide L17E (IWLTALKFLGKHAAKHEAKQQLSKL-amide). The investigators demonstrate that the peptide achieves cytosolic delivery primarily through transient plasma membrane disruption, bypassing some of the endocytic pathways, and highlight the pivotal role of the calcium-activated potassium channel KCa3.1, encoded by the gene KCNN4, in facilitating this process. These findings offer a deeper understanding of peptide-mediated delivery using a potassium channel and raise intriguing questions about …

Mergers And Acquisitions (M&As) In Pharmaceutical Markets: Associations With Market Concentration, Prices, Drug Quantity Sold, And Shortages, J. Daniel Mcgeeney M.S., Aylin Sertkaya Ph.D., Leah Ross M.A., Fred Ledley M.D., Cody Hyman Ph.D.

CISI Publication

In recent decades, the pharmaceutical industry has become increasingly concentrated in the United States, in part due to mergers and acquisitions (M&As) between drug manufacturers. This consolidation from M&As has been cited as a key factor affecting drug prices and drug shortages (U.S. Federal Trade Commission, 2022). In this study, we assessed trends in pharmaceutical M&As during 2010–2023 and evaluated the characteristics of drugs and companies involved in those M&As. We considered the effects of M&As on market concentration, drug prices, drug quantity sold, and drug shortages. We also considered how these associations vary by drug characteristics, including brand drugs …

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 …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Scaffolds With Spatiotemporally Controlled Growth Factor Delivery And Cyclodextrin-Enabled Antagonism Of Growth Factor Receptor Sequestration Promote Cutaneous Wound Healing, Jelena Marjanovic, Veronica Jurczuk, Lilian Valadares Tose, Yarixa Cintron Diaz, Francisco Fernandez Lima, Beatriz Abdo Abujamra, Sara Danker, Sinan Jabori, Devinder Singh, Jamie L. Burgess, Joshua Tam, Mohamadmahdi Samandari, Rivka C. Stone, Stephen C. Davis, Robert S. Kirsner, Marjana Tomic-Canic, Fotis M. Andreopoulos, Ivan Jozic

Mechanical & Aerospace Engineering Faculty Publications

Chronic wounds present a major burden to patients, health care professionals, and health care systems worldwide, yet treatment options remain limited and often ineffective. Although initially promising, growth factor-based therapies displayed limited and underwhelming effectiveness largely due to poor bioavailabilbioity and impaired receptor function within the chronic wound microenvironment. Here we demonstrate that chronic wounds exhibit elevated cholesterol synthesis, which disrupts growth factor signaling by sequestering receptors within lipid rafts. To address this, we developed a novel therapy combining growth factors with cyclodextrin in an ECM-mimetic scaffold, enabling localized cholesterol modulation and improved receptor accessibility. We demonstrate that this approach …