Pharmaceutics and Drug Design Commons^™

Seleksi Galur-Galur Leuconostoc Yang Mempunyai Aktivitas Bakteriostatin Terhadap Berbagai Bakteri Indikator, Agustina Retnaningsih, Amarila Malik, Maksum Radji

Majalah Ilmu Kefarmasian

Lactid Acid Bacteria (LAB) are known to produce bacteriocins which have antimicrobial activity, and possessed to be developed as antibiotic complement. This study aimed to characterize bacteriocins activity from Leuconostoc strains isolated previously from local sources, and to optimize pH and incubation temperature as well. A well diffusion agar assay for zone inhibition method and bacteriocin potency assay performing minimum inhibition concentration (MIC) have been done. Bacterial indicators used in this study are Leu. mesenteroides TISTR 120, and JCM 6124, Staphylococcus aureus FNCC 0047, Listeria monocytogenes FNCC 0156, Escherichia coli FNCC 0183, Pseudomonas aeruginosa FNCC 0063, Salmonella typhi FNCC 0165 …

Discovery Of Dihydroartemisinin And Dasatinib Drug Combination To Cure Pooroutcome Bcr-Abl+ Acute Lymphoblastic Leukemia, Harpreet Singh

Theses and Dissertations (ETD)

Oncogenic signaling by the Philadelphia chromosome-encoded BCR-ABL fusion kinase initiates and drives both Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Food and Drug Administration (FDA)- approved BCR-ABL-specific kinase inhibitors (BCR-ABL–KIs) imatinib, dasatinib and nilotinib induce prolonged remissions in CML but poor leukemia-reduction and relapse-control in Ph+ ALL. The relative primary BCR-ABL–KI-resistance in Ph+ ALL patients carrying predominantly BCR-ABLWT disease cannot be attributed to drug-resistant BCR-ABL mutations (BCR-ABLMUTANTS), and remains poorly understood.

We established a cell-based platform to evaluate the modulation of anti-Ph+ ALL activity of drugs by both tumor-extrinsic cytokines normally present in the leukemia …

Investigation Of Enhancement Of Furosemide Solubilization With Cyclodextrins And A Novel Octenyl Succinate Anhydride Starch, Rui Zhu

Theses and Dissertations (ETD)

Solubility behavior is one of the most challenging aspects for drug commercialization and often the main reason of drug that do not reach to its full potential. Now nearly 60% new chemical entities possess solubility problems, whereas practically no drug products with less than 10 µg/ml solubility in 70’s or 80’s. There is an ever increasing need to develop new formulation techniques and exicipients with novel mechanisms of action. Various techniques have been applied to enhance the drug solubility such as co-solvents, particle size reduction, lipid based drug delivery systems, nanosuspension, use of surfactants, salt formation, cyclodextrin complexes and solid …

Targeting Traf6 For Cancer Therapeutical Development, John K. Morrow

Dissertations and Theses (Open Access)

Tumor necrosis factor (TNF)-Receptor Associated Factors (TRAFs) are a family of signal transducer proteins. TRAF6 is a unique member of this family in that it is involved in not only the TNF superfamily, but the toll-like receptor (TLR)/IL-1R (TIR) superfamily. The formation of the complex consisting of Receptor Activator of Nuclear Factor κ B (RANK), with its ligand (RANKL) results in the recruitment of TRAF6, which activates NF-κB, JNK and MAP kinase pathways. TRAF6 is critical in signaling with leading to release of various growth factors in bone, and promotes osteoclastogenesis. TRAF6 has also been implicated as an oncogene in …

Hydrodynamic Effects Of An Arch-Shaped Fiber Optic Probe In A Dissolution Testing Apparatus 2, Yiran Zhang

Theses

Dissolution testing is widely used in the pharmaceutical industry to evaluate newly developed drug formulations and as a quality control method to insure that solid dosage forms have consistent dissolution property. Typically, samples are manually drawn from the dissolution vessel prior to analysis. An approach to overcome the limitations of manual sampling consists in the use of sampling probes, such as fiber optic probes, permanently inserted in the dissolution medium and continually sampling the drug concentration in it as the solid dosage form dissolves. Despite their advantages, permanently inserted fiber optic probes can alter the normal fluid flow within the …

P-Glycoprotein Functional Studies To Evaluate The Effect Of Cyclosporine Emulsion Formulations On Reversal Of Resistance In The Multidrug Resistant Cancer Cell Line Mes-Sa-Dx5, Katherine E. Cich

Undergraduate Honors Thesis Collection

Background: The overexpression of an efflux protein, p-glycoprotein (P-gp), is a leading cause of multi drug resistance (MDR). This research project is based on designing emulsions containing optimal doses of cyclosporine (CyA) and Pluronic® P-85 (P85), two agents found to be effective in inhibiting P-gp. Study

Objective: To investigate whether CyA exposure affects the quantity or functionality of P-gp in vitro.

Methods: To study the functionality of P-gp, MDR cells were incubated with CyA solutions containing the P-gp substrate and fluorescent dye Rhodamine 123 (RI23). P-gp inhibition was measured by fluorescence spectrophotometry, which indicates the accumulation of R123 inside the …

Investigations Of Pharmacokinetic Challenges In Premature Infants, Yi Zhang

Theses and Dissertations (ETD)

Premature infants (gestational age less than 37 weeks) are considered a vulnerable patient population due to their immaturity at birth. Currently, off-label prescribing is common in younger pediatric populations, especially in premature neonates and infants, which is a primary group receiving intensive care. Unique pharmacokinetic (PK) challenges—such as limited blood volume and frequency of blood sample collections, rapid growth and continuous developmental changes, complexity of pediatric studies as well as scientific, practical, and ethical concerns— lead to the current lack of PK information and empirical dosing in premature neonates and infants. In this research, several approaches were investigated to overcome …

Development Of Co-Processed Plasticized Cellulose Acetate For Sustained Release Matrix Tablets, Yinqi Zhou

Theses and Dissertations (ETD)

Cellulose Acetate (CA) is a polymer extensively used in pharmaceutical applications. Because of the hydrophobic nature and good film properties of CA, it is a good polymer candidate for sustained release matrix tablets. Sustained release matrix tablets of cellulose acetate can be prepared by direct compression or wet granulation methods. However, previous studies showed that a large amount of CA was required to achieve the desired sustained release profile for a sparingly soluble drug and it was difficult to formulate a highly water soluble drug by using CA as the retarding agent. Some studies concluded that CA is very sensitive …

Preclinical Study Of Potential Antiglioma Novel Tetrahydroisoquinoline Analogs: Pharmacokinetics And Mechanism Of Action, Fei Ma

Theses and Dissertations (ETD)

Gliomas, the tumors of glial cells, account for 80% of primary malignant brain tumors. In 2011, there were about 18,300 new cases of maligant gliomas in the United States alone. Patients with glioblastoma multiforme or anaplastic astrocytoma, the two major types of malignant gliomas, have a median survival of 14 months or 2 to 3 years, respectively. Therefore novel treatments for malignant glioma are urgently needed.

A novel series of tetrahydroisoquinoline derivatives with antiglioma activity has been undergoing drug metabolism/pharmacokinetics (DMPK)-guided lead optimization. EDL-291 was result from structure modification of last generation compound EDL-155. Its preclinical pharmacokinetics were characterized in …

The Histone Deacetylase Inhibitor, Ms-275, Sensitizes Metastatic Osteosarcoma To Fasl-Induced Cell Death: A Role For C-Flip, Krithi R. Bindal

Dissertations and Theses (Open Access)

The purpose of this study was to determine the effects of the histone deacetylase inhibitor, MS-275, on the Fas signaling pathway and susceptibility of osteosarcoma (OS) to Fas ligand (FasL)-induced cell death. OS metastasizes almost exclusively to the lungs. We have shown that Fas expression in OS cells is inversely correlated with their metastatic potential. Fas⁺ cells are rapidly eliminated when they enter the lungs via interaction with FasL, which is constitutively expressed in the lungs. Fas^- OS cells escape this FasL-induced apoptosis and survive in the lung microenvironment. Moreover, upregulation of Fas in established OS lung metastases …

Pengaruh Pemberian Infusa Herba Sambiloto (Andrographis Paniculata Nees) Terhadap Glibenklamid Dalam Menurunkan Kadar Glukosa Darah Tikus Putih Jantan Yang Dibuat Diabetes, Santi Purna Sari, Azizahwati Azizahwati, Diandra Andina Ratimanjari

Majalah Ilmu Kefarmasian

Many diabetics perform self-medication with antidiabetic herbs and synthetic drugs with the aim to obtain a synergistic or additive effects without informing their primary physician, such as the use of creat and glibenclamide. This research was carried out to know the impact of creat herb infusion on glibenclamide in bwering blood glucose levels on diabetic male albino rats. This study used 24 male Sparague-Lawley rats, which are divided into 6 groups, normal control and diabetic control were given 0,5% CMC solution I ml/200 g bw of rat, glibenclamide control were given glibenclamide suspension 0,9 mg/200 g bw of rat, creat …

Skrining Fitokimia Dan Uji Penghambatan Aktivitas Alfa-Glukosidase Pada Ekstrak Etanol Dari Beberapa Tanaman Yang Digunakan Sebagai Obat Antidiabetes, Abdul Munim, Azizahwati Azizahwati, Ayu Andriani

Majalah Ilmu Kefarmasian

Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglicemia and associated with abnormalities in carbohydrate, fat, and protein metabolisms. Patients with DM in the world continue to increase along with population growths. Starting from this condition, searching for sources of DM treatment is always performed. One therapy of DM is a-glucosidase inhibitor. a-Glucosidase is an enzyme that can break down a complex carbohydrate into simple sugar. lhe inhibiton of this enzyme can retard the rate of carbohydrate digestion resulting in a delay in glucose absorption. The purpose of this studywas to identify the content of chemical compound …

Archaeosomes And Tetraether Lipid Liposome, Hans-Joachim Freisleben

Majalah Ilmu Kefarmasian

Archaea have phytanyl ether lipids which is one of the characteristics that separates them from bacteria and eukaryotes. Some archaea have also unique membrane spanning tetrae ther lipids (T EL); in Sulfolobus and Ihermoplasma species these TELmake up the majority of total membrane lipids. Archaeal lipids are able to form stable liposomal structures, both from membrane factions, mainly the polar membrane fraction, i.e. archaeosomes, or from highly purified TEL (tetraether lipid liposomes). Liposomes of the main polar lipid (MPL) from thermoacidophilic archaeon Ihermoplasma acidophilum were thoroughly inevstigated. Archaeosomes and TEL liposomes exhibit extremely low proton permeability and high stability at …

Uji Penghambatan Aktivitas Alfa-Glukosidase Ekstrak Dan Fraksi Daun Antidesma Neurocarpum Miq., Rieka Widihasputri, Berna Elya, Azizahwati Azizahwati

Majalah Ilmu Kefarmasian

Diabetes mellitus is a metabolic dysfunction disease showed by hyperglicemia and abnormality of carbohydrates, fats, and proteins metabolism. It is known can be cured with a-glucosidase inhibitor. Previous experiment reported that methanol extract from leaves of Antidesma neurocarpum Miq. has a strong inhibitory activity of a-glucosidase (IC50 = 2,18 mikrogram/mL). The aim of this experiment was to know about the most active extract and fraction of inhibitory activity of a-glycosidase and also the chemical compounds from those most active extract and fraction. Extraction is done by using multilevel maceration (n-hexane, ethyl acetate and methanol). Inhibitory activity of a-glucosidase tested with …

Efek Antidiabetes Dan Identifikasi Senyawa Dominan Fraksi Kloroform Herba Ciplukan (Physalis Angulata L.), Sediarso Sediarso, Hadi Sunaryo, Nurul Amalia

Majalah Ilmu Kefarmasian

Antidiabetic activity of ciplukan (Physalis angulata L.) herb has been widely observed, as an extracts and infusions, proven to reduce blood sugar levels in rats or mice induced by alloxan. The research objective was to evaluate the antidiabetic effect and identify the content of the chloroform fraction ciplukan herb eluated with methanol-ammonia. Antidiabetic effects testing conducted using 30 male white mice (Mus musculus) ddY strain were divided into 6 groups, each consisting of 5 mice. K-1 is a negative control induced by alloxan, K-2, K-3 and K-4 induced by alloxan and treated with the test substance dose of 50 mg/kg …

Pengaruh Pemberian Sari Buah Mengkudu (Morinda Citrifolia Linn.) Terhadap Glibenklamid Dalam Menurunkan Kadar Glukosa Darah Tikus Putih Jantan Yang Dibuat Diabetes, Santi Purna Sari, Abdul Munim, Sri Wulandah Fitriani

Majalah Ilmu Kefarmasian

Drug interactions can occur in the use of two or more drugs simultaneously, including the use of synthetic drug with herbal medicine. Combination of glibenclamide with noni juice (Morinda citrifolia Linn.) often used by diabetic patient to decrease their blood glucose level. lhe aim of this research was to know the interaction between glibenclamide and noni juice administration on blood glucose level. This research used 24 Sprague-Dawley male rats which were divided into 6 groups. Before the experiment, the rats were first induced by alloxan, except group 1, which was the normal control. Group 2 was the control of diabetic …

Pharmacokinetic/Pharmacodynamic (Pk/Pd) Modeling Of Anti-Neoplastic Agents, Daniel Lexcen, Ahmed H. Salem, Walid F. Elkhatib, Virginia Haynes, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Development of tumor resistance to chemotherapeutics is related to inherent tumor variations regarding sensitivity to chemotherapeutics and to sub-optimal dosing regimens, including variation in patient pharmacokinetics that result in suboptimal exposure of tumor cells to anti-neoplastic drugs [1, 2]. The rate and extent of drug efficacy depends on the extent of drug exposure at the tumor site and the time above the effective concentration [3]. In vitro models that incorporate these pharmacokinetic and pharmacodynamic (PK/PD) principles to optimize therapeutic response may be considered the method of choice for optimizing dosing schedules before translating data from static assays to animals and …

Application Of Pharmacokinetics/Pharmacodynamics (Pk/Pd) In Designing Effective Antibiotic Treatment Regimens, Ghada F. Ahmed, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Designing antibiotic dosing regimens is often not optimal and the dose-response relationship for most antibiotics is not well-known1. Both Pharmacokinetics (PK) and Pharmacodynamics (PD) are characteristics of antimicrobial agents that should be considered in the development of effective antibiotic therapy. By linking the concentration time profile at the site of action to the drug effect (PK/PD), the effect of varying dosage regimens against pathogens could be simulated enabling the identification of effective dosage strategies. It is known that inadequate antibiotic dosing could not only lead to a therapeutic failure, but also to the development of bacterial resistance. Importantly, the evolution …

Inhibition Of Adhesion And Invasion Of Pseudomonas Aeruginosa To Lung Epithelial Cells: A Model Of Cystic Fibrosis Infection, Ayman Noreddin, Ghada Sawy, Walid Elkhatib, Ehab Noreddin, Atef Shibl

Pharmacy Faculty Books and Book Chapters

"Over their life time, CF patients experience multiple infections by various pneumoniacausing bacteria [6]. With more patients surviving to adulthood, chronic infections with Pseudomonas aeruginosa are coming to the forefront as a leading cause of death [7]. Problems presented by infected CF lung are multi-dimensional; the electrolyte balance and pH of the fluids are abnormal. The mucus is thick and of an alternative composition compared to normal lung and may contribute to colonization with Pseudomonas aeruginosa [2, 3, 5]. As such, research is multi-pronged and includes gene therapy to correct the defective protein, amelioration of inflammatory response and thinning of …

Preparation Of Different Polyamide Nanofiltration Membranes By Interfacial Polymerization And The Effect Of Post-Polymerization Treatment On Separation Performance, Yu Qin

Theses

Interfacial polymerization (IP) is a powerful technique for fabrication of thin film composite (TFC) membranes. In this study, polyamide nanofiltration (NF) composite membranes ware prepared by interfacial polymerization of polyethylenimine (PEI) or m-phenylene diamine (MPD) with isophthaloyl dichloride (IPD) on the surface of a porous polyethersulfone (PES) support. Concentrations of monomer reactants for this reaction were decided by equivalent weight ratio. A standard IP procedure was applied to successfully coat PES flat films. After preparation, three different post-polymerization treatments were employed and one optimal treatment was proven after membrane testing.

The TFC flat film membranes were characterized by nanofiltration of …