Pharmacology Commons^™

Development Of Targeted, Statin Loaded Nanoparticle Delivery Systems, Stephanie Judkins

Master's Theses

Statins lower endogenous production of cholesterol through their inhibition of the mevalonate pathway. Lipophilic statins in particular exhibit anti-inflammatory effects at supraphysiological doses by preventing downstream signaling through small molecule GTPases. Interest lies in development of statins as anti-inflammatory therapeutics, however, achieving effective doses locally incurs serious off-target effects. Our goal was to develop and optimize a targeted delivery system to traffic these drugs to inflamed sites and unload the drug at effective concentrations while avoiding systemic exposure. Lipophilic statins (lovastatin, simvastatin, and atorvastatin) were incorporated into polymeric nanoparticles (NPs) due to their hydrophobicity. We have shown that statins released …

Pharmacokinetics And Tissue Distribution Of A Lipid-Based Extended-Release Nano-Formulation Of Mo-Oh-Nap Tropolone To Enhance Pulmonary Delivery For The Treatment Of Pulmonary Metastatic Osteosarcoma, Wafaa N. Aldhafiri

Theses & Dissertations

Osteosarcoma is the most common primary bone tumor in children and adolescents. Metastasis is prevalent in 25% of patients, at diagnosis, with the lungs being the most common metastatic site. Pulmonary metastatic osteosarcoma is a significant therapeutic challenge with a 5-year survival rate of ≤30%. Patients with pulmonary metastatic disease at diagnosis receive the same standard of care as patients with local disease, which hasn’t changed over the past 30 years. The treatment and prevention of pulmonary metastatic osteosarcoma represents a significant critical and unmet need.

MO-OH-Nap tropolone is a novel small molecule with cytotoxic activity across multiple human osteosarcoma …

Bridging The Gap: Psychopharmacologic Education And Side Effect Screening For Non-Prescribing Mental Health Professionals, Elaine Fitzgerald

Dissertations

Abstract

Problem: The United States is experiencing a growing demand for pediatric mental health support. Surges in mental health diagnoses and psychotropic medication prescriptions have occurred, compounded by a shortage of psychiatric providers. Non-prescribing mental health professionals are well-positioned to recognize psychotropic medication side effects. However, psychologists and counselors lack formal pharmacology education.

Methods: The quality improvement (QI) initiative was guided by the Plan-Do-Study-Act (PDSA) model. The evidence-based psychopharmacologic education for non-prescribers utilized a quasi-experimental pre- and post- test design. Data collected from clinicians included knowledge, confidence, and skill concerning psychotropic medications. The Psychotropic Medication Monitoring Checklist (PMMC) screen clients …

T. Boudieri Extract Potentiates The Effects Of Capecitabine Treatment In Human Colon Cancer Cells, Katia Sawaya, Mahmoud Khalil, Ghada Khawaja

BAU Journal - Science and Technology

Resistance to chemotherapy remains a major challenge for colorectal cancer patients worldwide, hence the persistent need to uncover alternative treatments as well as new adjunct therapies in the fight against cancer. Natural extracts constitute an excellent source of bioactive substances that have a promising potential in that regard, with minimal negative side effects. We have previously demonstrated that both the ethanolic as well as the water extracts of Terfezia boudieri, a black desert truffle abundant in and part of the cuisine of the Mediterranean region, have significant antiproliferative effects against colon cancer cells. Our aim in this study was …

Fluorescent Carbon Nanodot-Based Rapid Cell Nucleus Staining And Application For Diagnosis, Daiming Zhong, Huamin Yuan, Qiuyan Tian, Gongping Deng, Yanhong Ouyang, Yi Chen, Yang Wang, Zhiqin Yuan

Journal of Food and Drug Analysis

Cell nucleus status decides the activities of corresponding cells, making its rapid and effective staining important for revealing the actual condition of biological environment in life science and related fields. In this study, fast staining of cell nucleus is realized by fluorescent carbon nanodots (CDs). The staining mechanism is due to the positively charged CD surface-induced cell membrane penetration, which facilitates the CD-nucleus binding via electrostatic attraction. The size of cell nucleus is easily measured with fluorescence imaging technique. In addition, the CD-based cell nucleus stain is applied for discriminating the normal and cancer cells by determining the cell-to-nucleus ratio …

Effects Of Ibuprofen In The Zdf Rat Model Of Type 2 Diabetes, Alexander Gosslau, Unsal Ozdogru, Emmanuel Zachariah, Shiming Li, Chi-Tang Ho

Journal of Food and Drug Analysis

We aimed to investigate the therapeutic potential of ibuprofen against type 2 diabetes (T2D) using obese Zucker diabetic fatty (ZDF) rats as type 2 diabetes model. ZDF rats were hyperglycemic, dyslipidemic and expressed pro-inflammatory markers in contrast to lean controls, thus reflecting the relationship between obesity and chronic inflammation promoting T2D. Chronic treatment with ibuprofen (2-(4-Isobutylphenyl)propanoic acid) was used to study the impact on pathological T2D conditions as compared to metformin (1,1-dimethylbiguanide) treated ZDF as well as lean controls. Ibuprofen decreased A1c but induced a high insulin release with improved glucose tolerance only after early time points (i.g., 15 and …

Citrus Depressa Peel Extract Act As A Prebiotic To Reduce Lipid Accumulation And Modulate Gut Microbiota In Obese Mice, Zheng-Yuan Su, Jie-An Liao, Ching-Ting Lin, Guor-Jien Wei, Yen-Chen Tung

Journal of Food and Drug Analysis

Citrus peels contain abundant polyphenols, particularly flavonoids, and have been shown to exert lipid accumulation decreasing ability. In this study, Citrus depressa peel applied to oven drying and extracted with ethanol extract as CDEE to analyze its flavonoids compositions and investigated its effects on a high-fat diet (HFD)-induced obese mice model. CDEE contained several flavonoids such as hesperidin, sinesentin, nobiletin, tangeretin, 5-demethylnobiletin, and 5-demethyltangeretin. The mice fed an HFD, and administration of 2% CDEE to could decrease weight gain, abdominal fat weight, inguinal fat weight, and the adipocyte size, and CDEE also reduced serum total cholesterol (TCHO), triacylglycerol (TG) compared …

Antityrosinase Activity And Lc-Ms/Ms Analysis Of Optimized Ultrasound-Assisted Condition Extracts And Fractions From Strawberry Tree (Arbutus Unedo L.), Serdar Demir, Halil Koyu, Mustafa Abdullah Yilmaz, Abbas Tarhan, Sura Baykan Ozturk

Journal of Food and Drug Analysis

Investigation of utilization possibilities of natural sources has been an important area for research. Tyrosinase inhibitory activity plays a key role in food and medicine industry. Strawberry tree (Arbutus unedo), a widely distributed plant among Mediterranean countries, possess fruits and leaves with rich bioactive phytochemicals, especially polyphenolic compounds. In this study, we aimed to investigate the antityrosinase activity of the fruit and leaf extracts of the plant, and to determine the phenolic compounds that contribute to the antityrosinase activity. In this regard, we evaluated the effect of solvent composition on the extraction of phenolic compounds from A. unedo …

Detection Of Aflatoxin B1 In Chili Powder Using Attenuated Total Reflectance–Fourier Transform Infrared Spectroscopy, Thin Thin Sein, Urairat Mongmonsin, Patutong Chatchawal, Molin Wongwattanakul, Oranee Srichaiyapol, Rungrueang Pattanakul, Patcharaporn Tippayawat

Journal of Food and Drug Analysis

Aflatoxin B₁, a major global food safety concern, is produced by toxigenic fungi during crop growing, drying, and storage, and shows increasing annual prevalence. This study aimed to detect aflatoxin B₁ in chili samples using ATR–FTIR coupled with machine learning algorithms. We found that 83.6% of the chili powder samples were contaminated with Aspergillus and Penicillium species, with aflatoxin B₁ levels ranging from 7.63 to 44.32 µg/kg. ATR–FTIR spectroscopy in the fingerprint region (1800−400 cm^-1) showed peak intensity variation in the bands at 1587, 1393, and 1038 cm^-1, which are mostly related …

Comparative Bioactivity Assessment Of Bixin Pigment And Associated Phytochemicals Extracted From Annatto Seeds Using Conventional And Green Solvents, Sonakshi Puri, Sumit Kumar Mandal, Harshit Jain, Pankaj Kumar Sharma, Perinkulam Ravi Deepa

Journal of Food and Drug Analysis

Nutraceuticals, that include food ingredients and bioactives from natural products, confer physiological health benefits and protection against chronic diseases. Annatto is a tropical shrub grown in Central and South America and parts of India. Its seeds are rich in the edible carotenoid-derived apocarotenoid pigment, bixin, which is used as a natural colorant in food, textiles, and cosmetics, and is now gaining attention for its potential health-promoting attributes. Here, we compared a green solvent (ethyl lactate) based extraction of bixin and associated metabolites in annatto seeds (crushed and seed coat) with two other conventional solvents (acetone and acid-base). Bixin was characterized …

Chemical Constituents From A Marine Medicinal Brown Alga-Derived Xylaria Acuta Sc1019, Hsiao-Yang Hsi, Shih-Wei Wang, George Hsiao, Li-Kwan Chang, Yuan-Chung Cheng, Shu-Jung Huang, Yi-Shan Lu, Tzong-Huei Lee

Journal of Food and Drug Analysis

In this study, a marine medicinal brown alga Sargassum cristaefolium-derived fungal strain Xylaria acuta SC1019 was isolated and identified. Column chromatography of the extracts from liquid- and solid-fermented products of the fungal strain was carried out, and led to the isolation of twenty-one compounds. Their structures were characterized by spectroscopic analysis, and the absolute configurations were further established by single X-ray diffraction analysis or modified Mosher’s method as nine previously undescribed compounds, namely xylarilactones A–C (1–3), ent-gedebic acid 8-O-α-D-glucopyranoside (4), 5R-hydroxylmethylmellein 11-O-α-D-glucopyranoside (5), ent …

The Role And Mechanism Of Cinnamaldehyde In Cancer, Jiahua Peng, Xin Song, Wenbin Yu, Yuhan Pan, Yufei Zhang, Hui Jian, Bin He

Journal of Food and Drug Analysis

As cancer continues to rise globally, there is growing interest in discovering novel methods for prevention and treatment. Due to the limitations of traditional cancer therapies, there has been a growing emphasis on investigating herbal remedies and exploring their potential synergistic effects when combined with chemotherapy drugs. Cinnamaldehyde, derived from cinnamon, has gained significant attention for its potential role in cancer prevention and treatment. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as …

Trends And Current Food Safety Regulations And Policies For Functional Foods And Beverages Containing Botanicals, Jarunee Intrasook, Takuji W. Tsusaka, Anil Kumar Anal

Journal of Food and Drug Analysis

Globally, the demand for functional foods and beverages has significantly increased due to socioeconomic changes, particularly in health consciousness to enhance their functionality. Functional ingredients derived from botanicals are widely used because of their phytochemical properties with health benefits. This study aims to (1) review the capabilities and challenges of botanical addition in functional foods, (2) review current policies and regulations for functional foods containing botanicals in the European Union (EU), Canada, Japan, the Republic of Korea, and Thailand, and (3) provide recommendations on effective food safety control measures for better consumer trust and trade facilitation. This critical review was …

Nanoparticles As Antioxidant Agents: A Comprehensive Review, Sulyman Olalekan Ibrahim, Halimat Yusuf Lukman, Fatimat Ronke Abdulkadir, Monsurat Yemisi Bello, Yusuf Oloruntoyin Ayipo, Halimah Funmilayo Babamale, Marili Funmilayo Zubair, Olubunmi Atolani

Al-Bahir

This study seeks to provide a comprehensive overview of the latest progress in the antioxidant properties of nanoparticles. Nanoparticles (NPs) have emerged as a promising tool in several domains of science and industry, including their application as antioxidant agents. The main knowledge gaps seem to be in correctly identifying the make-up of the naturally occurring phytochemicals that give these nano-antioxidants their extraordinary pharmacology and drug-like properties. In many instances, that characterization is done using spectroscopy instrumentation such as fourier-transform Infrared (FT-IR), scanning electron microscope (SEM), and X-ray diffraction analysis (XRD). From literature appraisals, it was discovered that a lot of …

A Drug's Life: The Untapped Potential Of Secondary Pharmacology Studies In Drug Development, Christina Scott

The University of New Hampshire Law Review

The United States Food and Drug Administration has evolved over the past century to regulate new medicine and protect the public from harmful or ineffective drugs. Drug development and testing science have advanced rapidly alongside the FDA’s increased regulation, enabling pharmaceutical companies to assess a drug's potential adverse reactions by studying its reactivity with various proteins called "off-target receptors." Off-target proteins are often screened and reported in the Investigational New Drug Application as a percentage indicating the drug's binding strength to each protein, which suggests the strength of a particular adverse drug effect. Adverse drug effects often lead to unfavorable …

The Multipurpose Dna Repair/Redox Protein Ape1 In Rodent And Human Lewy Body Disease, Kristin Marie Miner

Electronic Theses and Dissertations

Lewy body disorders are a family of neurodegenerative conditions characterized by proteostatic and redox disequilibrium, leading to deposition of the abundant protein α-synuclein in hallmark inclusions and oxidative damage to DNA. Sublethal oxidative DNA damage in neurons is repaired predominantly by the base excision repair pathway, which involves the coordinated activity of several enzymes, including apurinic/apyrimidinic endonuclease 1 (APE1). Despite emerging connections between α-synuclein, oxidative stress, and DNA damage/repair, along with evidence demonstrating the multifunctional nature of APE1, the link between APE1 and α-synuclein has not yet been explored.

Here, we conducted a broad investigation of APE1 in the context …

The Effect Of Novel Microtubule Modulators On Experimental Lewy Body Disease, Anuj S. Jamenis

Electronic Theses and Dissertations

In Lewy body disorders, α-synuclein aggregates are believed to destabilize the microtubular framework. However, microtubules are a challenging therapeutic target, as excessive rigidity or flexibility afforded by microtubule modulators may be neurotoxic. Thus, the objective of the present study was to evaluate dual-acting microtubule- stabilizing/destabilizing agents in cellular and animal models of early-stage Lewy body disease.

In Aim 1 we tested the dual-acting tricylic pyrimido[4,5-b]indole analogs AG161-47 and AG161-41 in an in vitro preformed fibril induced model of Lewy body disease. We found that both compounds reduced preformed fibril-seeded α-synucleinopathy without toxicity in primary hippocampal cultures. AG161-47 subtly impacted microtubule …

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …

An Ultra Long-Acting Bictegravir Prodrug Nanocrystal With A Shape-Shifting Pharmacokinetic Tail, Mohammad Ullah Nayan

Theses & Dissertations

While antiretroviral therapy (ART) has significantly reduced human immunodeficiency virus type one (HIV-1) co-morbidities and mortality, adherence to daily oral therapy remains a key barrier to all therapeutic and preventative outcomes. Over the past years, the emergence of long-acting (LA) ART has gained considerable enthusiasm amongst people living with HIV (PLWH) and could potentially simplify dosing regimens and improve treatment outcomes. LA ART could also improve drug adherence, reduce viral transmission, and limit viral drug resistance and systemic toxicities. In response to these needs, a combination of two LA injectable nanocrystalline drugs (CABENUVA) was recently approved for bimonthly administration in …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …