Pharmaceutics and Drug Design Commons^™

Delivery For Hydrophobic Drugs For Treating Pancreatic Cancer, Saud Almawash

Theses & Dissertations

Purpose The aim of this study was to determine whether coadministration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonategraft- dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice.

Methods P-DTX and P-CYP were synthesized from mPEGb- PCC through carbodiimide coupling reaction and characterized by 1H–NMR. The micelles were prepared by film hydration and particle size was measured by dynamic light scattering (DLS). Cytotoxicity, apoptosis and cell cycle analysis of P-DTX and P-CYP were evaluated in MIA PaCa-2 cells. In vivo efficacy …

Ocular, Neural, And Cellular Biodistribution Of Multifunctional Antioxidants, Damian Daszynski

Theses & Dissertations

Aging is a complex biological process which stems from a growing imbalance between the regenerative capacity of an organism and endogenous as well as exogenous damaging factors. This imbalance leads to the slow deterioration of individual cells, organs, and eventually the entire organism. The free radical theory of aging combines the evolutionary and mechanistic aspects of aging, postulating that the innate process is caused by deleterious, irreversible, and inevitable changes in biological systems caused by oxidative damage that accumulates over the lifespan. Evidence of this phenomenon is supported by the pathogenesis of age-related diseases, such as age-related macular degeneration and …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Gene Delivery To The Blood-Brain Barrier For Ischemic Stroke Therapy, Wanzhu Zhao

Electronic Theses and Dissertations

Stroke is a major cause of death in the United States. We aim to develop safe and efficient approaches for the treatment of stroke. Regenerative therapies have been identified as the major need for curing stroke [1]. We explored two different carriers (poly (ethylene glycol)_5k-poly (L-aspartate-diethylenetriamine)₄₈ (PEG-DET) / Pluronic P84 (P84) and exosomes (EXOs) / microvesicles (MVs)) to deliver brain-derived neurotrophic factor (BDNF) plasmid DNA (pDNA), a functional gene encoding a neurotrophin. In the first project, our data showed that DNA nanoparticles (NPs) with 0.03% P84 was a promising formulation to deliver Luciferase pDNA into immortalized human …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Phenylpyrazalopyrimidines As Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, And Molecular Simulations, Bhupender S. Chhikara, Sajda Ashraf, Saghar Mozaffari, Nicole St. Jeans, Dindyal Mandal, Rakesh Kumar Tiwari, Zaheer Ul-Haq, Keykavous Parang

Pharmacy Faculty Articles and Research

N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC₅₀ = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% …

The Effects Of An Adenosine A(2a) Agonist As An Adjunctive Treatment To Alleviate Sensorimotor Gating Deficits In A Rodent Model Of Schizophrenia, Hannah Rauhuff

Undergraduate Honors Theses

The adenosine system has become a promising target for the treatment of schizophrenia due to its unique relationship with dopamine D₂ receptors. Dopamine D₂ receptors display heightened sensitivity in schizophrenia, and inhibition of these receptors has been shown to alleviate some of the psychotic symptoms of the disorder. Inhibition of adenosine A(2A) receptors has been shown to decrease dopamine D₂ receptor sensitivity, making this receptor a potential target for treatment of the disorder. This effect occurs because adenosine A(2A) receptors form a mutually inhibitory heterodimeric complex with dopamine D₂ receptors. The present study looked at the …

Characterization Of Novel Cb2 Agonist Smm-295 And Its Effects In Ischemia/Reperfusion Injury, Jeffrey D. Pressly

Theses and Dissertations (ETD)

Acute kidney injury (AKI) is a major problem clinically affecting up to two-thirds of intensive care unit patients, and results in increased hospitalization time, the risk of developing chronic kidney disease, and mortality. Hallmarks of AKI include tubular cell death and a decrease in renal perfusion which leads to decreases in renal function following injury. For 20 years the pathophysiology of AKI has been well established. However, therapies for AKI have shown minimal to no success clinically. The work here describes our efforts to further categorize the effects of CB2 activation, a possible novel therapeutic target in AKI.

There is …

Assessment Of Depression Among Older Adults Staying In Old Home Care In Klang, Malaysia, Muhammad Qamar, Nurul Zahirah, Sohail Ahmad

Pharmaceutical Sciences and Research

Mental disorders such as depression are widespread, often underdiagnosed, and usually inappropriately treated. The early recognition of factors that may promote depression with the help of depression screening aid can help to plan better care for the patient. Therefore, this study aimed to determine the depression prevalence among the older adults staying in old home care, to explore any association and differences of depression across various socio-demographic variables, and to study the predictors of depression among study subjects. A cross-sectional study was conducted with a convenience sample of 141 elderly by using the validated tool. The study instrument was divided …

Encapsulation Of Temulawak Extract By Using Nanocrystalline Cassava And Sago Starches And Maltodextrin, Titi Candra Sunarti, Fatimah J. Pasaribu, Christina Winarti

Pharmaceutical Sciences and Research

This study was conducted to evaluate the performance of Curcuma zanthorrhiza crude extract after encapsulated in nanocrystalline starch, and to investigate the effect of the ratio of nanocrystalline starches and maltodextrin; and the effect of concentration of temulawak extract on nanocapsule characteristics, as well as encapsulation effect on the stability of antioxidant activity. Preparation of nanocrystalline starch was conducted by using lintnerization and ethanol precipitation of cassava and sago starches. Nanocrystalline starch and maltodextrin were used as matrices with the ratio varied from 25:75, 50:50, and 75:25. The mixture of temulawak extract and matrices were homogenized and spray dried. Nanocapsules …

An Exploration Of Electrospun Fibers Containing Drug-Cyclodextrin Inclusion Complexes, Fatimah Fatimah, Zeynep Aytac, Tamer Uyar, George Pasparakis, Gareth R. Williams

Pharmaceutical Sciences and Research

A series of new core-shell fibers were developed containing anticancer drugs (5-fluorouracil or ferulic acid) and their cyclodextrin inclusion complexes, with a gadolinium-based magnetic resonance imaging (MRI) contrast agent. These were prepared by electrospinning, a simple method for producing ultra-fine fibers through the application of a strong electrostatic force on a polymer solution. The shell of the fibers was formed from Eudragit S100, and the drugs were loaded in the core. Scanning electron microscopy images showed the formation of smooth ribbon-like fibers, with diameters ranging from 1.4 to 5.1 μm, and transmission electron microscopy reveals a transparent interface between the …

Formulasi Gel Ekstrak Daun Kelor (Moringa Oleifera Lamk) Sebagai Sediaan Antiinflamasi, Nining Sugihartini, Syauqul Jannah, Tedjo Yuwono

Pharmaceutical Sciences and Research

The development of anti-inflammatory gel of Moringa oleifera leaf extract has been performed. This study aimed to determine the physical properties, irritation index and anti-inflammatory activity of gel with various concentration of Moringa oleifera leaf extract. The extract was obtained by maceration method using ethanol 70%. The extracts were formulated in a gel with a concentration of 3%, 6%, 9% by using Carbopol 940 as gelling agent. The gel was evaluated for its physical properties (viscosity, pH, spreadability, adhesivity), irritation index with rabbit test animals and anti-inflammatory activity with mice test animals based on epidermal thickness parameters. The test results …

Evaluation Of Potential Drug Interaction Of Analgesic In Cancer Patient Receiving Palliative Care In Dharmais Cancer Hospital, Eme Stepani Sitepu, Atika Wahyu Puspitasari, Nuriza Ulul Azmi, Lila Nilam Sari

Pharmaceutical Sciences and Research

Analgesics are mostly used in cancer patients receiving palliative care to improve the quality of life of patients. Besides analgesics, cancer patients receiving palliative care were also given other drugs in combination to overcome other symptoms of cancer, and this combination could potentially cause drug interactions. This study was aimed to analyze the potential of drug interactions with analgesics in cancer patients. The study design was cross-sectional with a retrospective method and descriptive study. The sample of this study was cancer palliative care patient’s prescription at Dharmais Cancer Hospital in the period of January – December 2017. The sample analyzed …

Profil Terapi Antihipertensi Dan Antihiperlipidemia Terhadap Fungsi Ginjal Pasien Diabetes Melitus Tipe 2 Dengan Komplikasi Penyakit Ginjal Kronis Di Rsup Dr. Hasan Sadikin, Fitri Rachmaini, Lia Amalia, Cherry Rahayu

Pharmaceutical Sciences and Research

Chronic Kidney Disease (CKD) complication increases the risk of morbidity and mortality in type 2 diabetes mellitus (DMT2) patients. The presence of hypertension and dyslipidemia as comorbidity increases the risk of macrovascular and microvascular complications and further adding to the list of drugs used. Management of this comorbidity is essential to prevent cardiovascular events and minimize kidney damage. This study aimed to evaluate therapeutic profile of antihypertensive and antihyperlipidemia drugs towards kidney function in DMT2 patients with CKD complication at Dr. Hasan Sadikin Hospital. Study was done by using a prospective single cohort design with consecutive sampling technique and obtained …

Interaction Of Thymidine With Sodium Bis(2-Ethylhexyl) Sulfosuccinate In Alcohol And Water: Studies With Uv-Vis Technique, Indu M. Paudel, Ajaya Bhattarai

Pharmaceutical Sciences and Research

The accurate measurement of thymidine absorbance in the presence of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in ethanol and water systems at room temperature by UV-vis technique has been reported. The AOT concentrations varied from 0.0005 to 0.014 [mol/L] in ethanol whereas from 0.0002 to 0.042 [mol/L] in water. The concentration of thymidine was 0.0073 [mol/L] during UV-vis spectrum registration. The thymidine spectrum was examined in the presence of AOT concentration. Using a statistical method of non-linear regression (NLREG), thymidine binding and thymidine distribution constants were evaluated. A noticeable decrease in thymidine absorbance in the presence of AOT concentration was shown in …

Development Of Ethanolic Extract Of Pinang Masak Jambi (Areca Catechu L.) As A Modulator Of Doxorubicin Cytotoxic Effect In Breast Cancer Therapy, Fitrianingsih Fitrianingsih, Indri Maharini, Diah Tri Utami

Pharmaceutical Sciences and Research

Doxorubicin is one of the chemotherapy agents that is often used in breast cancer therapy. Phenomenon of breast cancer cell resistance to chemotherapy agents has been traced to the molecular level. The development of compounds that can overcome drug resistance chemotherapy needs to be continuously developed, especially agents with specific molecular targets, namely P-glycoprotein (Pgp), NFkB, cyclin, and cyclin-dependent kinase (CDK). Another alternative is the combination of chemotherapy agents with chemopreventive agents (co-chemotherapy) to reduce side effects and increase sensitivity of cancer cells. Doxorubicin is often used in breast cancer therapy. This study was performed to determine the effect of …

Anti-Proliferative Effects Of A Coumarin Benjaminin On Four Human Cancer Cell Lines, Siau Hui Mah, Soek Sin Teh, Ahmad Azri Fitri Ismail, Gwendoline Cheng Lian Ee

Pharmaceutical Sciences and Research

Cancer is a major health issue around the globe. Chemotherapy and radiation therapy are no longer the standard treatments for patients as these remedies lead to many adverse effects. Thus, the development of alternative effective drugs from lead compounds, especially natural products is necessary. This study aimed to isolate cytotoxic phytochemical constituents from a plant Calophyllum inophyllum, which has been used as traditional medicine since ancient time. The root of C. inophyllum was extracted and subjected for phytochemical constituent isolation. A coumarin, benjaminin (1) was isolated successfully from the chloroform extract and its structural elucidation was performed by spectroscopy analyses …

Ace Inhibitory Activity And Functional Group Analysis Of Solvent- Partitioned Fractions Of Eleusine Indica, Jade Celon Cometa, Liahona Faith Roldan Mancol, Anthony Nalzaro Yen, Joanne Katherine Talens Manlusoc

Pharmaceutical Sciences and Research

Eleusine indica Linn. Gaerth or Indian goose grass has been widely used as an alternative natural anti-hypertensive agent. However, the rationale behind this mechanism is still unknown. The purpose of this study is to confirm the presence of functional groups that may be responsible for its ACE inhibitory activity and its possible synergism. Each solvent-portioned fraction was analyzed by FTIR, individual ACE inhibitory activity, and combination of fractions. FTIR results of solvent- partitioned fractions revealed that O-H and C-H stretches were present in all fractions. In addition to this, C-O and C=O groups were also present in all fractions except …

Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …