Pharmaceutics and Drug Design Commons^™

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 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 …

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 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% …

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 …

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 …

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) …

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 …

Aktivitas Antioksidan Ekstrak, Fraksi Dan Golongan Senyawakimia Daun Premna Oblongata Miq, Katrin Katrin, Atika Bendra

Pharmaceutical Sciences and Research

Indonesia has many kinds of plants which can be used as natural antioxidant sources. This study was focused on antioxidant activity of Cincau Perdu leaves extract (Premna oblongata Miq.) using 1-Diphenyl-2-picrylhydrazyl (DPPH) methods. P. oblongata leaves was extracted using n-hexane, ethylacetate and methanol. It was found that methanol extract has the highest activity with IC50 value 20.01 μg/mL. The extract with highest antioxidant activity were fractionated with accelerated column chromatography and were earned 6 combination fractions. The antioxidant activity of each combination fractions were tested by DPPH methods. Fraction-5 showed the highest activity as antioxidant with IC50 23.51 μg/mL. The …

Pengaruh Kandungan Komponen Minor Dari Minyak Kelapa Sawit (Elaeis Guineensis Jacq.) Terhadap Aktivitas Antioksidan Pada Proses Pemurnian Karotenoid, Ahmad Gazali Sofwan Sinaga, Donald Siahaan

Pharmaceutical Sciences and Research

Palm oil contains carotenoid and vitamin E which possess antioxidant properties. A long exposure of heat and chemical substances during the purification process may lower antioxidant activity. This research was conducted to compare antioxidant activity of carotenoid and vitamin E obtained from each stage of three continuous purification process (transesterification, solvolytic micellization, and saponification). Total carotenoid concentration was analyzed by UV-visible spectrophotometer at λ 446 nm and total vitamin E concentration was analyzed by high-performance liquid chromatography, while ester and triglyceride concentration were analyzed by gas chromatography. Antioxidant activity was measured by DPPH assay with incubation time in 60 minutes. …

Evaluasi Kadar Kurkumin Dalam Jamu Tradisional Kunir Asam Yang Dijual Di Pasar Kota Gede Bulan Februari 2015, Fitrilya Mustikahati Yusuf, Nurkhasanah Nurkhasanah

Pharmaceutical Sciences and Research

Javanese women often consume kunir asam to relieve dysmenorrhea symptom. It is a traditional herbal medicine which is conventionally prepared from curcuma domestica. One of the active compound of curcuma domestica is curcumin. The purpose of this research is to determine the amount of curcumin available in kunir asam selling in daily market of Kota Gede. Curcumin level in daily batches consistency was also evaluated. Curcumin analysis was conducted by qualitative and quantitative tests by TLC densitometry method. A total of 50.0 ml kunir asam was extracted with 25.0 ml of chloroform, and then the mixture was dried by evaporation. …

Toksisitas Ekstrak Etanol Mangifera Foetida L. Sebagai Pengkelat Besi Ditinjau Dari Ld50 Dan Komponen Sel Darah, Tri Wahyuni, Santi Purna Sari, Ari Estuningtyas, Hj Freisleben

Pharmaceutical Sciences and Research

Ethanolic extract of bacang mango leaves (Mangifera foetida L.) decreased iron concentration in blood Sprague dawley rats that had been induced iron overload. The aim of this experiment was to determine acute toxicity (LD50) value of ethanolic extract of M.foetida by weil method and its effect to blood component. This study was conducted by employing a complete random design using 25 male and 25 female mice of DDY strain which devided into 5 groups. The first group until fourth group were administered ethanolic extract of M.foetida with dose variation which suspension in aquadest orally. The fifth group was control that …

Evaluasi Aktivitas Antioksidan Senyawa 4-[(E)-2-(4-Okso-3-Fenilkuinazolin-2-Il)Etenil]-Benzensulfonamida Dan Analognya, Catur Jatmika, Baitha Palanggatan Maggadani, Hayun Hayun

Pharmaceutical Sciences and Research

Quinazolinone derivative compounds exhibit a broad spectrum of biological activity, including antioxidant. Quinazolinone derivative compound 4-[(E)-2-(4-oxo-3-phenyl quinazolin-2-yl)ethenyl]-benzensulfonamida and its analogs (2a-f) have been synthesized and demonstrated its activity as a selective inhibitor of cyclooxygenase-2. The aim of this research was to evaluate the antioxidant activity of compound 4-[(E) -2-(4-oxo-3-fenilkuinazolin-2-yl)ethenyl]-benzensulfonamida and its analogs with DPPH radical scavenging method, ferric reducing activity potential (FRAP), and phosphomolybdenum method. The experiment revealed that the % inhibition and antioxidant capacity of compound 2c, 2e and 2f were higher compared to compound 2a, 2b and 2d. The DPPH radical scavenging analysis found that the % inhibition …

Sintesis Dan Karakterisasi Hidrogel Superabsorben Kitosan Poli(N-Vinilkaprolaktam) (Pnvcl) Dengan Metode Full Ipn (Interpenetrating Polymer Network), Nadhrah Wivanius, Emil Budianto

Pharmaceutical Sciences and Research

Polymer material used for hydrogel should have capability to swell and to keep water molecules in its structure without solubilised in water. Natural polymers has functional groups which can perform as active sites in modification to produce polymer with better characteristic. Chitosan is a natural polymer which has good swelling ability but lack of structural strength. Synthesis of chitosan hydrogel by interpenetrating polymer network (IPN) will increase its strength through crosslinking. In this research, the first step of modification was the synthesis of chitosan polymer network crosslinked by acetaldehyde. The next step was the synthesis of PNVCL polymer network crosslinked …