Pharmaceutics and Drug Design Commons^™

Uji Toksisitas Fraksi Air Impatiens Balsamina Pada Tikus Betina Galur Sprague Dawley, Entang Nurqolbiah, Indri Kusharyanti, Siti Nani Nurbaeti

Pharmaceutical Sciences and Research

The present study was aimed to predict the level of toxicity of aqueous fraction of Impatiens balsamina by acute toxicity study using OECD guideline 425. Female Sprague Dawley 8-12 week and weight between 140-170 gram were used, the amount of experimental rats were 10 rats. Rats were sequentially administered all the fraction in single dosage (limit test) of 2000 mg/kg body weight and 5000 mg/kg of body weight. All the animals were individually studied for mortality, wellness parameters, food consumption,water consumption, body weight. Histopathological examination was done on the liver and kidney. The result of this study showed that no …

Formulasi Gel Pacar Air (Impatiens Balsamina Linn.) Terhadap Propionibacterium Acnes Dan Staphylococcus Epidermidis, Diah Ismarani, Liza Pratiwi, Indri Kusharyanti

Pharmaceutical Sciences and Research

Acnes vulgaris is a chronic inflammatory disease of sebaceous follicles caused by Propionibacterium acnes and Staphylococcus epidermidis. The antibacterial activity of Impatiens balsamina L. has been studied for many years. The aims of this study are to find out the antiacne effect from methanolic extract of stems and leaves of Impatiens balsamina L. that formulated in gel. Simplicia were extracted using soxhlet technique bu using methanol as solvent. Extracts were then formulated in gel in three variations of HPMC 4000 and Carbopol 934 as gel base with ratio of 70:30 (F1), 50:50 (F2) and 30:70 (F3). The determination of antiacne …

Pengaruh Natrium Hialuronat Terhadap Penetrasi Kofein Sebagai Antiselulit Dalam Sediaan Hidrogel, Hidroalkoholik Gel, Dan Emulsi Gel, Joshita Djajadisastra, Zuraida Syafara Dzuhro, Sutriyo Sutriyo

Pharmaceutical Sciences and Research

Anticellulite topical gel preparation with caffeine as active ingredient needs a penetration enhancer to reach subcutaneous layer. Sodium hyaluronate (NaHA), the sodium salt of hyaluronic acid, is a hydrophilic polysaccharide derivative polymer. It has ability to enhance percutaneous penetration by loosening the dense of the compact substance stratum corneum. The aim of this research was to observe the effects of NaHA on caffeine penetration as anticellulite active agent in three types of gel preparation: hydrogel, hydroalcoholic gel, and gel emulsion. Each gel type contained caffeine 1,5% and was varied into three formulas. Formula 1 contained HPMC 2% as gel basis; …

An Introduction To Drugs And The Neuroscience Of Behavior, Adam J. Prus

Books

This up-to-date text provides an introductory overview of the nervous system actions and behavioral effects of the major classes of psychoactive drugs, using pedagogy unique among pharmacology texts to make the topic approachable.

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within The First 7 Days Of Therapy Associated With Acute Kidney Injury In Children?, Chad A. Knoderer, Kristen R. Nichols, Kelsey C. Lyon, Megan M. Veverka, Amy C. Wilson

Scholarship and Professional Work – COPHS

Background In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development.

Methods Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic …

Cinacalcet Administration By Gastrostomy Tube In A Child Receiving Peritoneal Dialysis, Kristen R. Nichols, Chad A. Knoderer, Bethanne Johnston, Amy C. Wilson

Scholarship and Professional Work – COPHS

A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient’s therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole.

Facile, Regio-And Diastereoselective Synthesis Of Spiro-Pyrrolidine And Pyrrolizine Derivatives And Evaluation Of Their Antiproliferative Activities, Abdulrahman I. Almansour, Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Chen, Brian Sullivan, Kellen Mccaffrey, Alaa Nahhas, Keykavous Parang, Mohamed Ashraf Ali

Pharmacy Faculty Articles and Research

A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 M) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-alpha-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds …

Synthesis And Evaluation Of Antiproliferative Activity Of Substituted N-(9-Oxo-9h-Xanthen-4-Yl)Benzenesulfonamides, Somayeh Motavallizadeh, Asal Fallah-Tafti, Saeedeh Maleki, Amir Nasrolahi Shirazi, Mahboobeh Pordeli, Maliheh Safavi, Sussan Kabudanian Ardestani, Shaaban Asd, Rakesh Tiwari, Donghoon Oh, Abbas Shafiee, Alireza Foroumadi, Keykavous Parang, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed …

Effects Of Hepatic Ischemia-Reperfusion Injury On The P-Glycoprotein Activity At The Liver Canalicular Membrane And Blood-Brain Barrier Determined By In Vivo Administration Of Rhodamine 123 In Rats, M. K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker.

Methods Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis.

Results P-gp protein …

Nanoparticle Encapsidation Of Flock House Virus By Auto Assembly Of Tobacco Mosaic Virus Coat Protein, Payal D. Maharaj, Jyothi K. Mallajosyula, Gloria Lee, Phillip Thi, Yiyang Zhou, Christopher M. Kearney, Alison A. Mccormick

Faculty Publications & Research of the TUC College of Pharmacy

Tobacco Mosaic virus (TMV) coat protein is well known for its ability to self-assemble into supramolecular nanoparticles, either as protein discs or as rods originating from the ~300 bp genomic RNA origin-of-assembly (OA). We have utilized TMV self-assembly characteristics to create a novel Flock House virus (FHV) RNA nanoparticle. FHV encodes a viral polymerase supporting autonomous replication of the FHV genome, which makes it an attractive candidate for viral transgene expression studies and targeted RNA delivery into host cells. However, FHV viral genome size is strictly limited by native FHV capsid. To determine if this packaging restriction could be eliminated, …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Multi-Component Microparticulate/Nanoparticulate Dry Powder Inhalation Aerosols For Targeted Pulmonary Delivery, Xiaojian Li

Theses and Dissertations--Pharmacy

The aim of the work was to design, manufacture, and characterize targeted multi-component dry powder aerosols of (non-destructive) mucolytic agent (mannitol), antimicrobial drug (tobramycin or azithromycin), and lung surfactant mimic phospholipids (DPPC:DPPG=4:1 in molar ratio). The targeted dry powder for inhalation formulation for deep lung delivery with a built-in rationale of specifically interfering several disease factors of chronic infection diseases in deep lungs such as cystic fibrosis, pneumonia, chronic bronchitis, and etc. The dry powder aerosols consisting of selected chemical agents in one single formulation was generated by using spray drying from organic solution.

The physicochemical properties of multi-component dry …

Human Butyrylcholinesterase Mutants For Cocaine Detoxification, Shurong Hou

Theses and Dissertations--Pharmacy

Cocaine is one of the most reinforcing drugs of abuse and has caused serious medical and social problems. There is no FDA-approved medication specific for cocaine. It is of a high priority to develop an effective therapeutic treatment for cocaine abuse. Human butyrylcholinesterase (BChE) has been recognized as a promising candidate of enzyme therapy to metabolize cocaine into biologically inactive metabolites and prevent it from reaching central nervous system (CNS). However, the catalytic activity of wide-type human BChE against cocaine is not sufficiently high for treatment of cocaine abuse. Dr. Zhan’s lab has successfully designed and discovered a series of …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Simultaneous Bactericidal And Osteogenic Effect Of Nanoparticulate Calcium Phosphate Powders Loaded With Clindamycin On Osteoblasts Infected With Staphylococcus Aureus, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

S aureus internalized by bone cells and shielded from the immune system provides a reservoir of bacteria in recurring osteomyelitis. Its targeting by the antibiotic therapy may thus be more relevant for treating chronic bone infection than eliminating only the pathogens colonizing the bone matrix. Assessed was the combined osteogenic and antibacterial effect of clindamycinloaded calcium phosphate nanoparticles of different monophasic compositions on co-cultures comprising osteoblasts infected with S aureus. Antibiotic-carrying particles were internalized by osteoblasts and minimized the concentration of intracellular bacteria. In vitro treatments of the infected cells, however, could not prevent cell necrosis due to the …

Nanoparticulate Drug Delivery Platforms For Advancing Bone Infection Therapies, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Introduction—The ongoing surge of resistance of bacterial pathogens to antibiotic therapies and the consistently aging median member of the human race signal an impending increase in the incidence of chronic bone infection. Nanotechnological platforms for local and sustained delivery of therapeutics hold the greatest potential for providing minimally invasive and maximally regenerative therapies for this rare but persistent condition.

Areas covered—Shortcomings of the clinically available treatment options, including poly(methyl methacrylate) beads and calcium sulfate cements, are discussed and their transcending using calcium-phosphate/polymeric nanoparticulate composites is foreseen. Bone is a composite wherein the weakness of each component alone is …

Electrostatic Charge Effects On Pharmaceutical Aerosol Deposition In Human Nasal-Laryngeal Airways, Jinxiang Xi, Xiuhua Si, Worth Longest

University Faculty Publications and Creative Works

Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the upper airways, where particles come in close proximity to the narrow turbinate surface, and before charge dissipation occurs as a result of high humidity. The objective of this study was to quantitatively evaluate the deposition of charged aerosols in an MRI-based nasal-laryngeal airway model. Particle sizes of 5 nm-30 μm and charge levels ranging from neutralized to …

In Vitro Analysis Of Nanoparticulate Hydroxyapatite/Chitosan Composites As Potential Drug Delivery Platforms For The Sustained Release Of Antibiotics In The Treatment Of Osteomyelitis, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, …

Investigating Intermolecular Interactions In Crystalline Aspirin Using Cdft, Nicholas Turner, Tonglei Li, Mingtao Zhang

The Summer Undergraduate Research Fellowship (SURF) Symposium

Drugs today are widely administered in their crystalline form, namely via tablets and capsules. The crystal structure of a drug molecule affects important drug qualities such as solubility, bioavailability, shelf life, and compaction properties. In order to form a basis for crystal structure prediction, it is necessary to first understand how intermolecular interactions cause molecules to pack in certain ways. Being able to predict and perhaps even control a drug molecule’s crystal structure will lead to the development of higher quality drugs that perform more consistently. Scientists and engineers do not fully understand the reasons for a molecule assuming a …

Effects Of Short-Term Portacaval Anastomosis On The Peripheral And Brain Disposition Of The Blood-Brain Barrier Permeability Marker Sodium Fluorescein In Rats, Imam H. Shaik, M. K. Miah, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Contradictory results have been reported with regard to the effects of various models of hepatic encephalopathy on the blood-brain barrier (BBB) permeability, which may be due partly to the use of brain concentrations of BBB markers without attention to their peripheral pharmacokinetics. The purpose of the current study was to investigate the effects of short-term portacaval anastomosis (PCA), a type B model of hepatic encephalopathy, on the peripheral pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a small molecule marker of BBB passive permeability. A single 25 mg/kg dose of FL was administered intravenously to 10-day PCA and …