Pharmaceutics and Drug Design Commons^™

Daun Jambu Biji (Psidium Guajava L.) Sebagai Antikanker Payudara, Dwitiyanti Dwitiyanti

Pharmaceutical Sciences and Research

Guava leaves are used as a cytotoxic. Previous research has demonstrated that guava leaves contained 61.71% of quersetin and has potential as an cytotoxic. The aim of this study was to determine the cytotoxic activity of 70% ethanol extract of guava leaves against cancer cells T47D. The method used direct counting (viable cell count) to obtained LC50 value. This study used a test solution with six concentrations that were 130.62; 67.98; 35.98; 18.43; 9.56 and 5 µg/ml. The LC50 value from the 70% ethanol extract of guava leaves was 27.54 µg/ml. The results suggested the extract of guava leaves has …

Enzim Papain: Aspek Green Chemistry Pada Reaksi Knoevenagel, Laurentius Haryanto, Antonius Herry Cahyana

Pharmaceutical Sciences and Research

Green chemistry aspect is the chemical approach that has been studied in the past two decade. One of the principles is the development of green synthesis process that is friendly for the environment. This research showed that papain can be used as catalyst for Knoevenagel reaction with 3 kinds of substituted-benzaldehyde and malononitrile as substrates in aqueous medium. The best reaction condition with 80% yield was reached by utilizing of 25 mg papain/mmol substrate. Reaction was conducted at ambient temperature and pressure for 30 min. Products were as yellowish to yellow needle crystals and successfully characterized by melting point, UV-Vis, …

Uji Toksisitas Akut Dan Efek Antiinflamasi Ekstrak Metanol Dan Ekstrak N-Heksana Daun Pepaya (Carica Papaya L), Tahara Dilla Santi

Pharmaceutical Sciences and Research

The acute toxicity test and antiinflammatory effect of methanolic and n-hexane extracts Carica papaya L leaf have been studied. The results of phytochemical screening show that papaya leaf contains alkaloid, steroid, and flavonoid compound. Flavonoid and alkaloid extracted from methanolic extract of papaya leaf and steroid extracted from n-hexane extract of papaya leaf. The acute toxicity test of methanolic and n-hexane extracts Carica papaya L leaf have been studied on rat with giving a single dose of samples. The aim of this work was to investigate the behavioral responses (pharmacological profile), the development of body weight and mortality for 14 …

Skrining Fitokimia Dan Aktivitas Antioksidan Fraksi Etanol Alga Merah Eucheuma Spinosum, Bina Lohita Sari, Nurulia Susanti, Sutanto Sutanto

Pharmaceutical Sciences and Research

The red alga, Eucheuma spinosum from South Bangka Waters was shown to contain antioxidant activity. Natural antioxidants from algae are known to play an important role against various diseases and aging processes. The study objective was to investigate phytochemical screenings and antioxidant activity of ethanol fractions Euchema spinosum from south Bangka waters. Antioxidant activities of fresh algae (FA), dry algae (DA), and algae product (AP) were determined with DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Extraction was conducted using 70% ethanol in acidic environment for 24 hours. Then, the extract was evaporated using rotary evaporator. Dry extract was fractionated with ethanol - n - …

Application Of Ichip To Grow “Uncultivable” Microorganisms And Its Impact On Antibiotic Discovery, Rinzhin T. Sherpa, Caretta J. Reese, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Purpose. Antibiotics have revolutionized modern medicine, allowing significant progress in healthcare and improvement in life expectancy. Development of antibiotic resistance by pathogenic bacteria is a natural phenomenon; however, the rate of antibiotic resistance emergence is increasing at an alarming rate, due to indiscriminate use of antibiotics in healthcare, agriculture and even everyday products. Traditionally, antibiotic discovery has been conducted by screening extracts of microorganisms for antimicrobial activity. However, this conventional source has been over-used to such an extent that it poses the risk of “running out” of new antibiotics. Aiming to increase access to a greater diversity of microorganisms, …

Polymeric Nanocarriers For Treatment Of Melanoma And Genetically Modified Mesenchymal Stem Cells To Improve Outcome Of Islet Transplantation, Vaibhav Mundra

Theses & Dissertations

Melanoma is a lethal malignancy with limited treatment options for advanced metastatic stages. New targeted therapeutic options with discovery of BRAF and MEK inhibitors have shown significant survival benefit. Despite the recent progress, inefficient tumor accumulation and dose limiting systemic toxicity remains pressing challenges for treating metastatic melanoma and there is a need for drug delivery approach to improve therapeutic index of chemotherapeutics. Nanoparticle based drug delivery represents promising approach to enhance efficacy and reduce the dose limiting systemic toxicity. Nanoparticles can be formulated either by physical encapsulation of drugs or by covalent conjugation of drugs to the polymeric backbone. …

Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation, Vivek Mahajan

Theses & Dissertations

Non-ionic amphiphilic block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronics, arranged in a tri-block structure PEO-PPO-PEO, have raised a considerable interest in skeletal muscle Gene Therapy. Previous studies have demonstrated that co-administration of Pluronics with naked plasmid DNA (pDNA) by direct i.m. injection enhanced transgene expression not only in muscle but also in distal lymphoid organs (spleen and lymph nodes) and this response was strain-dependent; not observed in athymic (BALB/c nu/nu) mouse; suggesting a role of immune cells in gene transfer to skeletal muscles. Therefore, we first evaluated the role of inflammation and inflammatory cells, on muscle …

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

Dissertations and Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential …

Overcoming Acquired Resistance To Braf Inhibitors By Novel Synergistic Drug Combination And Discovery Of Novel Smac Mimetics As Selective Survivin Inhibitors, Jin Wang

Theses and Dissertations (ETD)

The first part (Chapter 1 and 2) of this dissertation presents a novel combination study of melanoma therapy. Acquired clinical resistance to vemurafenib, a selective BRAFV600E inhibitor, arises frequently after short term chemotherapy. Since the inhibitions of targets in the RAFMEK-ERK pathway result in G0/G1 cell cycle arrest, vemurafenib-resistant cancer cells are expected to escape this cell cycle arrest and progress to subsequent G2/M phase. We hypothesized that a combined therapy using vemurafenib with a G2/M phase blocking agent will trap resistant cells and overcome vemurafenib resistance. To test this hypothesis, we first determined the combination index (CI) values of …

Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-Fang Zhang, Meng Cui, Diomedes E. Logothetis

Pharmacy Faculty Articles and Research

Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

Experimental Determination Of The Agitation Requirements For Solids Suspension In Dissolution Systems Using A Mini Paddle Apparatus, Yang Song

Theses

Dissolution testing is a critical step in quality control of manufactured final products in the pharmaceutical industry. The United State Pharmacopeia (USP) Dissolution Testing Apparatus 2 (paddle) is the most widely used dissolution test devices in the pharmaceutical industry to formulate solid drug dosage forms and to develop quality control specifications for its manufacturing process.

Mini vessels and mini paddle dissolution testing systems are smaller versions of the USP 2 Apparatus. The concept of the mini paddle apparatus is similar to that of the USP 2 setup but it is scaled down about to 1/5 of the volume and 40% …

Effect Of Impeller Submergence On Power Dissipation And Solids Suspension In Mixing Systems Equipped With Pitch-Blade Turbines, Yufeng Song

Theses

Mixing and dispersion of solids in a liquid is a process frequently encountered in the pharmaceutical industry and often conducted in cylindrical baffled tanks stirred by mechanical impellers. In operations where the liquid level is decreased (as often which emptying the tank) the process must be stopped when the solids are no longer suspended. In this work, the minimum agitation to suspend solids (Njs) when the liquid level was lowered, and the impeller submergence S_b changed as a result were determined for the case of a six-blade, pitch-blade turbine (6-PBT) impeller. The power consumed by the impeller …

Experimental Determination Of Solids Suspension With Angled Impeller In A Pharmaceutical Mixing Vessel, Yingxi Tang

Theses

Angled-mounted impellers are commonly used in a number of pharmaceutical industry applications, from laboratory reactors to full-scale tanks. In these systems, the impeller is not centrally and vertically mounted, as in most stirred vessels, but it enters the vessel, and is therefore immersed in the fluid, at an angle from the vertical. This arrangement provides some baffling effects that would not otherwise exist if the impeller was centrally mounted.

One common requirement for such systems is that they are capable of suspending small solids dispersed in the liquid. Therefore, it is critical to know the value of the minimum agitation …

Analyzation Of Metabolic Reprogramming In Drug-Resistant Mcf-7 Cells, Derick Han, Ho Leung, Andrew Vo

Student Scholar Symposium Abstracts and Posters

The Warburg effect states that cancer cells mainly receive their energy from anaerobic glycolysis. Thus, mitochondria play a different role in the metabolism of cancer cells as opposed to normal, healthy cells. In chemotherapy, there is always a chance of the cancer regressing. Making drug-resistant cancer cells to analyze their metabolism may change how cancer is treated. This study aimed to create drug-resistant MCF-7 cell lines with doxorubicin in order to determine the metabolic changes that have occurred in the process of becoming resistant to drug treatments.

Clinical Applications Of A Combination Chemotherapy Using 8-Chloro Camp And 8-Chloro Adenosine, Erik Munoz, Andrea Saich, Andrew Cox, Yu-An Peter Chang

Student Scholar Symposium Abstracts and Posters

Dr. Cho-Chung from the NIH first thought to use halogenated cAMP derivatives as competitive inhibitors of cAMP to slow down cancer cell mitosis. While the iodine and bromine substituted versions showed very little therapeutic actions, 8-Chloro cAMP has been shown to have strong anti-cancer effects. This has been shown in the phase II clinical trials this drug has undergone. However, these trials have had issues with solubility and toxicity. The drug is similar to vitamin C and is excreted quickly. Scientists tried to overcome this by using a peristaltic pump to give patients a continuous dosage, but this proved too …

Periodontal Disease: Molecular Visualization Through Computer Modeling And 3d Printing, Catherine Chatowsky

Senior Honors Projects

Periodontal disease is a common infection that damages gingival tissue and creates jawbone destruction that can lead to the loosening or loss of teeth. Hundreds of diverse bacterial species reside in the harsh environment of the oral cavity. The creation of plaque and biofilms serve to allow the bacteria to avoid immune-mediated destruction. This project analyzed periodontal disease pathogens using molecular printing 3D visualization. Two bacterial species (T. denticola and P. gingivalis) were chosen from the public resource: Research Collaboratory for Structural Bioinformatics: Protein Data Bank. T. denticola was a bacteria found to have a binding protein (FhbB) …

The Effects Of Rhein And Thymoquinone On Obesity And Diabetes In Diet-Induced Obese Mice., Emily Martell

Senior Honors Projects

Natural product extracts and chemicals isolated from natural products (e.g. plants, berries, seeds) have been commonly used in various types of traditional medicines. In addition, some drugs on the market today have been derived from natural product sources. The purpose of our study was to evaluate two natural products, Rhein and Thymoquinone, for as potential anti-diabetic and anti–obesity agents. According to the Center for Disease Control (CDC), the number of people in the US diagnosed with diabetes has increase from 11.9 million people in the year 2000 to 20.8 million people in the year 2011. Rhein is a natural compound …

Design, Development And Evaluation Of Erlotinib-Loaded Hybrid Nanoparticles For Targeted Drug Delivery To Nonsmall Cell Lung Cancer, Bivash Mandal

Theses and Dissertations (ETD)

The objective of this work was to design, develop and evaluate erlotinib-loaded coreshell type lipid albumin hybrid nanoparticles (CSLAHNPs) for targeted drug delivery to nonsmall cell lung cancer (NSCLC). Erlotinib (ETB) is a highly selective, potent and reversible inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR) which is overexpressed (50-90%) in NSCLC. ETB is marketed as film coated tablets for oral delivery. However, poor survival rate along with life-threatening adverse effects were reported from oral administration. Nanoparticulate delivery system of ETB might be advantageous to target the tumor cells, thereby increasing therapeutic efficacy and reducing off-targeting toxicities of ETB …

Design, Development, Characterization And Testing Of Cd22 Targeted Long Circulating Liposomal Drug Delivery Systems For B Cell Malignancies, Nivesh Kumar Mittal

Theses and Dissertations (ETD)

Hematological malignances of the B cells affect almost 130,000 people in the United States every year of which approximately 44,000 lose their lives. Therapies for B cell malignancies such as doxorubicin, have limitations due to dose related adverse effects such as neutropenia and cardiomyopathy. AD 198 is a novel PKC-delta activating agent that has cytotoxic superiority over doxorubicin by being able to circumvent resistance mechanisms developed by the cancer cells towards doxorubicin and being cadioprotective from the damage caused to cardiomyocytes by doxorubicin. Targeted delivery of AD 198 is crucial to moderate the non-specific interactions of the chemotherapeutic agent with …