Medicinal and Pharmaceutical Chemistry Commons^™

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 …

Development Of Tunable Rose Bengal Based-Nanogumbos As Potential Selective Chemotherapeutic Agents, William J.A. Russell

Honors College Theses

As cancer remains one of the greatest threats to the global population, the development of chemotherapeutic agents that are selective and tunable is of critical importance. Herein, a series of Rose Bengal (RB)-based GUMBOS, a group of uniform materials based on organic salts, were synthesized via counterion exchange between [Na]₂[RB] and three organic cations: tetrabutylphosphonium bromide [TBP][Br], tetraphenylphosphonium chloride [TPP][Cl], and 1-dodecyl-3-methylimidazolium chloride [C₁₂MIm][Cl]. The resulting GUMBOS were characterized through FT-IR, ESI-MS, NMR, and UV-Vis Spectroscopy. Partition coefficient studies indicated all GUMBOS exhibited hydrophobic physiochemical characteristics. These hydrophobic RB-based GUMBOS …

Developing Curcumin Analogues For Treating Breast Cancer, Tulasi Laxmi Nutalapati

Theses, Dissertations and Capstones

Breast cancer is still one of the most common types of cancer and one of the most common causes of cancer-related deaths in women around the world. Despite significant advances in early detection and treatment strategies, drug resistance, systemic toxicity, and poor outcomes in aggressive subtypes continue to limit the overall effectiveness of cancer therapy. Natural compounds have become promising anticancer agents because they can target many different things and are not very toxic. Curcumin has shown promise as an anticancer drug, but it cannot be used in the clinic because it does not absorb well, breaks down quickly, and …

Metabolomics Driven Discovery Of Bioactive Natural Products Leads From Marine And Terrestrial Sources For The Development Of Analgesics, Sahar Mofidi Tabatabaei

University of Kentucky Doctoral Dissertations

Natural products remain a rich source of structurally diverse bioactive compounds for drug discovery, particularly for pain therapeutics. However, the chemical complexity of natural product extracts presents significant challenges for the efficient identification and prioritization of bioactive metabolites. This dissertation integrates untargeted LC-MS/MS-based metabolomics, molecular networking, classical natural products chemistry, and neurobiological assays to accelerate the discovery of analgesic lead compounds targeting the emerging pain-associated receptor σ₂R/TMEM97.

An untargeted metabolomics workflow was developed to systematically profile complex biological extracts and guide bioactive compound isolation. High-resolution LC-MS/MS data were analyzed using molecular networking (GNPS/GNPS2) to visualize chemical space, dereplicate known metabolites, …

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 …

Formulation Development Of Topical Inserts Containing Doxycycline And Doxycycline Combined With Tenofovir Alafenamide And Elvitegravir For The Prevention Of Sexually Transmitted Infections, Vivek Agrahari, M. Melissa Peet, Jasmin Monpara, Rijo John, Sriramakamal Jonnalagadda, Pardeep K. Gupta, Meredith R. Clark, Gustavo F. Doncel

CONRAD Publications

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 …

Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

LDL receptor related protein 1 (LRP1) is a major hepatic receptor involved in lipoprotein metabolism, protease degradation, transmembrane receptor modulation, and clearance of excess protein, such as Aβ. Decreased expression of LRP1 due to liver injury can impair receptor-mediated clearance, increasing Aβ availability in the periphery. We investigated the effects of hepato-specific silencing of LRP1 on Aβ deposition in the brain. Additionally, other LDL family members (LRP5, LRP6, and LDLR) that may participate in Aβ clearance were monitored in the liver to ensure non-compensatory effects of LRP1 silencing.

Method

4-month-old male double transgenic (APP/PS1) AD mice were injected with …

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Isolation And Antibacterial Evaluation Of Bioactive Compounds From Mussaenda Philippica A.Rich.: A Bioassay-Guided Approach, M. Rifqi Efendi, Mesa Sukmadani Rusdi, Muhammad Iqbal, Ilham Padavi, Sri Indah Pirmawati, Deddi Prima Putra

The Thai Journal of Pharmaceutical Sciences

Background: Mussaenda philippica A.Rich. (commonly known as Nusa Indah in Indonesia), a member of the Rubiaceae family, has been traditionally used throughout Southern Asia to treat various ailments, including bacterial infections, inflammation, ulcers, and liver disorders. These medicinal uses are particularly associated with its bark, leaves, sepals, and root. Objectives: This study aimed to isolate and identify bioactive compounds from M. philippica white modified sepals using a bioassay-guided approach and evaluate their antibacterial activity.
Materials and Methods: The study consisted of four main stages: (i) methanol extraction and liquid–liquid partitioning of M. philippica sepals; …

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 …

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 …

Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, n = 4–5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma …

The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

Background

Injury-repair responses typically induce tissue or organ scarring. Generally, cAMP-mobilizing agents inhibit the activation of fibroblasts and deposition of extracellular matrix. Some but not all cAMP-mobilizing agents inhibit fibrosis. Evidence suggests that inhaled treprostinil, a prostacyclin (IP) analog, increases intracellular cAMP levels [cAMP]I, and slows the decline in pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the molecular mechanisms by which cAMP-mobilizing agents, including treprostinil, alter the expression of matrix proteins in human lung fibroblasts (HLF) remain unclear. Unlike other Gαs -coupled receptors, we posit that the antifibrotic properties of treprostinil are driven by cAMP-mobilizing-dependent and -independent …

Evaluation Of Hypolipidemic And Hypoglycemic Effects Of Dillenia Indica L. On Alloxan-Induced Diabetic Rats, Md Mahfuj Alam Siddiq

Student Scholarship

Context: Dillenia indica L. a tropical fruit-bearing plant native to South and Southeast Asia, has attracted scientific interest due to its rich phytochemical composition and potential therapeutic benefits in managing diabetes, lipid disorders, and oxidative stress. Objective: The objective of this study was to investigate the potential antidiabetic and lipid-lowering properties of D. indica fruit and bark extracts in a rat model of alloxan-induced type 2 diabetes. Methods: Diabetes was induced in rats using an intraperitoneal injection of alloxan (160 mg/kg) after a 12-hour fast. The chloroform fractions of D. indica fruit and bark (200 mg/kg) were administered intraperitoneally, with …

Phytochemisty And Antioxidant Activity Of Ethanol, Ethyl Acetate, And N-Hexane Extracts Of Suruhan Leaves (Peperomia Pellucida), Ade Arsianti, Steven Gill, Diyah Kristanty

Indonesian Journal of Medical Chemistry and Bioinformatics

Background: Free radicals are natural byproducts of cellular metabolism, in which, their excessive accumulation can lead to oxidative stress, which plays a key role in the development of various chronic diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Antioxidants are compounds capable of scavenging free radicals and minimizing oxidative damage. Peperomia pellucida, commonly known as Suruhan leaves, is a tropical herb traditionally used in folk medicine that contain bioactive compounds correlated with a strong radical-scavenging activity, suggesting its potential as a natural antioxidant source. This study aims to conduct a phytochemical analysis and evaluate the antioxidant activity of ethanol, …

Inflammation And Detection: Rethinking The Biomarker Landscape In Gastric Cancer, Keykavous Parang, Koosha Paydary

Pharmacy Faculty Articles and Research

Gastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that …

Quality By Design Approach To Method Development And Validation For Quantitative Estimation Of Dapagliflozin And Linagliptin In Pharmaceutical Tablet Dosage Forms, Prechha Shrestha, Ashwinee Kumar Shrestha, Rajan Shrestha, Barsha Thapa

The Thai Journal of Pharmaceutical Sciences

Objectives: The present study utilizes a quality by design approach to develop a simple, robust, and stability-indicating high-performance liquid chromatography method for quantifying dapagliflozin (DAPA) and linagliptin (LINA) in a fixed-dose combination and validate it according to the ICH-Q2 (R1) guidelines.

Materials and Methods: The effect of critical method parameters (CMPs), namely percentage of acetonitrile (ACN), pH of the buffer, and flow rate, on critical quality attributes (CQAs) such as retention time, area, tailing factor, and theoretical plates was studied using Box–Behnken design (BBD). Response optimizer was utilized to optimize the experimental conditions. The mobile phase (MP) consisted of ACN …

Editorial: Molecular Mechanisms Of Ion Channel Activation And Modulation, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

"Ion channels are integral membrane proteins that regulate the passage of ions across cell membranes, thereby shaping processes as diverse as neuronal signaling, muscle contraction, and hormone secretion. Channel activation is typically initiated by a stimulus such as voltage, ligand binding, or mechanical stress that induces conformational changes and opens the channel pore. Beyond activation, channels are subject to fine-tuned modulation by a wide range of endogenous and exogenous agents, from lipids and neurotransmitters to pharmacological drugs. Modulators can stabilize the open, closed, or inactivated states, shift ligand affinities, or alter gating kinetics. Dissecting the structural and dynamic basis of …

Clinical Pharmacokinetics, Pharmacodynamics, And Drug Interactions Of Remimazolam, Derek E. Murrell, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Remimazolam, an ultrashort-acting benzodiazepine, has emerged as a promising sedative agent for procedural sedation and general anesthesia. It combines the favorable properties of traditional benzodiazepines with a rapid onset and offset of action, largely due to its unique metabolism via hepatic carboxylesterases rather than cytochrome P450 enzymes. This metabolism allows for predictable pharmacokinetics, reducing the risk of prolonged sedation and drug accumulation, particularly in patients with hepatic or renal impairment. Clinically, remimazolam demonstrates non-inferiority to midazolam and propofol, with advantages including a lower incidence of hypotension and respiratory depression. Multiple randomized controlled trials have shown its efficacy in various procedural …