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Sample records for b-adrenergic drugs improves

  1. IMPROVING ACCESS TO DRUGS

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2012-11-01

    Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs

  2. Trafficking of α1B-adrenergic receptor mediated by inverse agonist in living cells

    Institute of Scientific and Technical Information of China (English)

    MingXU; Ying-huaGUAN; NingXU; Zhang-yiLIANG; Shu-yiWang; YaoSONG; Chi-deHAN; Xin-shengZHAO; You-yiZHANG

    2005-01-01

    AIM The project is aimed at understanding the action of inverse agonist at single molecule level and capturing the real time picture of molecular behavior of α1B-adrenergic receptor (AR) mediated by inverse agonist in living cells by single molecule detection (SMD). METHODS The location and distribution of α1B-AR was detected by laser confocal and whole cell 3H-prazosin binding assay. Dynamic imaging of BODIPY-FL-labeled prazosin (Praz), specific antagonist of (1-AR, was observed in α1B-AR stably expressed human embryonic kidney 293 (HEK293) living cells. The detection of real-time dynamic behaviors of AR was achieved by using fluorescence-labeled AR and its ligand combined with SMD techniques. RESULTS α1B-AR was predominantly distributed on the cell surface and 8.2% of the total receptors were located in cytosol.

  3. The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence.

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    Fabrice Trovero

    Full Text Available Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg and cyproheptadine (1 mg/kg (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France and cyproheptadine (1 mg/kg could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs.

  4. GENETIC VARIATION IN THE ALPHA1B - ADRENERGIC RECEPTOR AND VASCULAR RESPONSE

    Science.gov (United States)

    Adefurin, Abiodun; Ghimire, Laxmi V.; Kohli, Utkarsh; Muszkat, Mordechai; Sofowora, Gbenga G.; Li, Chun; Levinson, Rebecca T.; Paranjape, Sachin Y.; Stein, C. Michael; Kurnik, Daniel

    2016-01-01

    α1B- adrenergic receptors contribute to vasoconstriction in humans. We tested the hypothesis that variation in the ADRA1B gene contributes to interindividual variability and ethnic differences in adrenergic vasoconstriction. We measured dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 41 African-Americans and genotyped 34 ADRA1B variants. We validated findings in another model of catecholamine-induced vasoconstriction, the increase in mean arterial pressure (ΔMAP) during a cold pressor test (CPT). One ADRA1B variant, rs10070745, present in 14 African-American heterozygotes but not in Caucasians, was associated with a lower phenylephrine ED50 (geometric mean [95% CI], 144 [69–299] ng/ml) compared to 27 African-American non-carriers (208 [130–334] ng/ml; P=0.015) and contributed to the ethnic differences in ED50. The same variant was also associated with a greater ΔMAP during CPT (P=0.008). In conclusion, ADRA1B rs10070745 was significantly associated with vasoconstrictor responses after adrenergic stimulation and contributed to the ethnic difference in phenylephrine sensitivity. PMID:27089938

  5. Nanosizing techniques for improving bioavailability of drugs.

    Science.gov (United States)

    Al-Kassas, Raida; Bansal, Mahima; Shaw, John

    2017-08-28

    The poor solubility of significant number of Active Pharmaceutical Ingredients (APIs) has become a major challenge in the drug development process. Drugs with poor solubility are difficult to formulate by conventional methods and often show poor bioavailability. In the last decade, attention has been focused on developing nanocrystals for poorly water soluble drugs using nanosizing techniques. Nanosizing is a pharmaceutical process that changes the size of a drug to the sub-micron range in an attempt to increase its surface area and consequently its dissolution rate and bioavailability. The effectiveness of nanocrystal drugs is evidenced by the fact that six FDA approved nanocrystal drugs are already on the market. The bioavailabilities of these preparations have been significantly improved compared to their conventional dosage forms. There are two main approaches for preparation of drug nanocrystals; these are the top-down and bottom-up techniques. Top-down techniques have been successfully used in both lab scale and commercial scale manufacture. Bottom-up approaches have not yet been used at a commercial level, however, these techniques have been found to produce narrow sized distribution nanocrystals using simple methods. Bottom-up techniques have been also used in combination with top-down processes to produce drug nanoparticles. The main aim of this review article is to discuss the various methods for nanosizing drugs to improve their bioavailabilities. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Overview on gastroretentive drug delivery systems for improving drug bioavailability.

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    Lopes, Carla M; Bettencourt, Catarina; Rossi, Alessandra; Buttini, Francesca; Barata, Pedro

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

  7. alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse.

    Science.gov (United States)

    Doze, Van A; Handel, Evelyn M; Jensen, Kelly A; Darsie, Belle; Luger, Elizabeth J; Haselton, James R; Talbot, Jeffery N; Rorabaugh, Boyd R

    2009-08-18

    Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive-compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of alpha(1)-adrenergic receptors (alpha(1)-ARs). Yet, it is unclear whether increased alpha(1)-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant alpha(1A)-ARs (CAM alpha(1A)-AR) or CAM alpha(1B)-ARs were used to examine the effects of alpha(1A)- and alpha(1B)-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM alpha(1A)-AR mice, but not CAM alpha(1B)-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective alpha(1)-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an alpha(1A)-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM alpha(1A)-AR mice but not in CAM alpha(1B)-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM alpha(1A)-AR, and CAM alpha(1B)-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that alpha(1A)- and alpha(1B)-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that alpha(1A)-ARs may be a useful therapeutic target for the treatment of depression.

  8. α1A- and α1B-Adrenergic Receptors Differentially Modulate Antidepressant-Like Behavior in the Mouse

    Science.gov (United States)

    Doze, Van A.; Handel, Evelyn M.; Jensen, Kelly A.; Darsie, Belle; Luger, Elizabeth J.; Haselton, James R.; Talbot, Jeffery N.; Rorabaugh, Boyd R.

    2009-01-01

    Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of α1-adrenergic receptors (α1-ARs). Yet, it is unclear whether increased α1-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant α1A-ARs (CAM α1A-AR) or CAM α1B-ARs were used to examine the effects of α1A- and α1B-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM α1A-AR mice, but not CAM α1B-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective α1-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an α1A-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM α1A-AR mice but not in CAM α1B-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM α1A-AR, and CAM α1B-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that α1A- and α1B-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that α1A-ARs may be a useful therapeutic target for the treatment of depression. PMID:19540213

  9. Improving the Tuberculosis Drug Development Pipeline

    OpenAIRE

    Evangelopoulos, D; McHugh, T D

    2015-01-01

    Mycobacterium tuberculosis is considered one of the most successful pathogens and multidrug-resistant tuberculosis, a disease that urgently requires new chemical entities to be developed for treatment. There are currently several new molecules under clinical investigation in the tuberculosis (TB) drug development pipeline. However, the complex lifestyle of M. tuberculosis within the host presents a barrier to the development of new drugs. In this review, we highlight the reasons that make TB ...

  10. Augmenting drug-carrier compatibility improves tumour nanotherapy efficacy

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    Zhao, Yiming; Fay, François; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L.; Goode, Brandon; Duivenvoorden, Raphaël; de Lange Davies, Catharina; Bjørkøy, Astrid; Weinstein, Harel; Fayad, Zahi A.; Pérez-Medina, Carlos; Mulder, Willem J. M.

    2016-04-01

    A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug-carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug-carrier compatibility affects drug release in a tumour mouse model. We found the drug's hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug's compatibility; as a result, we achieved better antitumour efficacy. Our results help elucidate nanomedicines' in vivo fate and provide guidelines for efficient drug delivery.

  11. Metabolomics has the potential to improve drug therapy

    DEFF Research Database (Denmark)

    Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder

    2014-01-01

    Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even mor...... "individualized". In this chase metabolomics is a hot topic. The aim of this paper is to review the concepts of metabolomics and the possible applications in regard to drug development, drug therapy and diagnosis, prognosis and monitoring of diseases....

  12. THE POLYMORPHISM OF Α2B-ADRENERGIC RECEPTOR GENE — A NEW GENETIC MARKER OF THE HEREDITARY SICK SINUS SYNDROME

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    S. Iu. Nikulina

    2010-01-01

    Full Text Available Aim. To study the association of the hereditary sick sinus syndrome (SSS with gene α2B-adrenergic receptor (ADRA2B polymorphism.Material and methods. 29 families with hereditary primary SSS from the database of the Chair of Therapy № 1 of Krasnoyarsk State Medical University named after prof. V.F. Voyno-Yasenetsky were included in the study. Group 1 included probands (20 women and 9 men, 58±0.15 y.o., group 2 – proband relatives of I, II and III degree (65 males and 68 females, 39±0.13 y.o., group 3 (control — 89 healthy volunteers. Clinical examination (physical examination, ECG, bicycle ergometry, ECG monitoring, atropine test, electrophysiological study, echocardiography was performed in all probands and their relatives. The diagnosis of SSS was confirmed by transesophageal left atrium stimulation in 75 individuals. Genotypic examination of gene ADRA2B I/D polymorphism was performed in 213 individuals: 75 SSS-patients, 49 their healthy relatives, 89 healthy volunteers.Results. 3 types of ADRA2B genotypes (II — homozygous wild, ID — heterozygous, DD — homozygous mutant were founded by allele-specific polymerase chain reaction. Significant prevalence of the homozygous genotype of more rare alleles DD in SSS-patients (28±5.2% compared to the control group (8.99±3.0% was found.Conclusion. Study of the genetic marker can be used to identify predisposition to hereditary SSS in the population and individual-family level. SSS due to mutations in genes that regulate cell function of sinus node and the sinoatrial conduct occurs, apparently, extremely rarely.

  13. Synergistic drug combinations improve therapeutic selectivity

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    Lehàr, Joseph; Krueger, Andrew S.; Avery, William; Heilbut, Adrian M.; Johansen, Lisa M.; Price, E. Roydon; Rickles, Richard J.; Short, Glenn F.; Staunton, Jane E.; Jin, Xiaowei; Lee, Margaret S.; Zimmermann, Grant R.; Borisy, Alexis A.

    2009-01-01

    Prevailing drug discovery approaches focus on compounds with molecular selectivity, inhibiting disease-relevant targets over others in vitro. However in vivo, many such agents are not therapeutically selective, either because of undesirable activity at effective doses or because the biological system responds to compensate. In theory, drug combinations should permit increased control of such complex biology, but there is a common concern that therapeutic synergy will generally be mirrored by synergistic side-effects. Here we provide evidence, from 94,110 multi-dose combination experiments representing diverse disease areas and large scale flux balance simulations of inhibited bacterial metabolism, that multi-target synergies are more specific than single agent activities to particular cellular contexts. Using an anti-inflammatory combination, we show how multi-target synergy can achieve therapeutic selectivity in animals through differential target expression. Synergistic combinations can increase the number of selective therapies using the current pharmacopeia, and offer opportunities for more precise control of biological systems. PMID:19581876

  14. Drug utilisation study in a tertiary care center: Recommendations for improving hospital drug dispensing policies

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    Niti Mittal

    2014-01-01

    Full Text Available Drug therapy accounts for a major portion of health expenditure. A useful strategy for achieving cost efficient healthcare is drug utilisation research as it forms the basis for making amendments in drug policies and helps in rational drug use. The present observational study was conducted to generate data on drug utilization in inpatients of our tertiary care hospital to identify potential targets for improving drug prescribing patterns. Data was collected retrospectively from randomly selected 231 medical records of patients admitted in various wards of the hospital. WHO Anatomical Therapeutic Chemical/Defined Daily Dose methodology was used to assess drug utilisation data and drug prescriptions were analysed by WHO core drug indicators. Antibiotics were prescribed most frequently and also accounted for majority of drug costs. The prescribed daily dose for most of the antibiotics corresponded to defined daily dose reflecting adherence to international recommendations. Brand name prescribing and polypharmacy was very common.78% of the total drugs prescribed were from the National List of Essential Medicines 2003. Restricting the use of newer and costlier antibiotics, branded drugs and number of drugs per prescription could be considered as targets to cut down the cost of drug therapysignificantly.

  15. Improving drug manufacturing with process analytical technology.

    Science.gov (United States)

    Rodrigues, Licinia O; Alves, Teresa P; Cardoso, Joaquim P; Menezes, José C

    2006-01-01

    Within the process analytical technology (PAT) framework, as presented in the US Food and Drug Administration guidelines, the aim is to design, develop and operate processes consistently to ensure a pre-defined level of quality at the end of the manufacturing process. Three PAT implementation scenarios can be envisaged. Firstly, PAT could be used in its most modest version (in an almost non-PAT manner) to simply replace an existing quality control protocol (eg, using near-infrared spectroscopy for an in-process quality control, such as moisture content). Secondly, the use of in-process monitoring and process analysis could be integrated to enhance process understanding and operation for an existing industrial process. Thirdly, PAT could be used extensively and exclusively throughout development, scale-up and full-scale production of a new product and process. Although the first type of implementations are well known, reports of the second and third types remain scarce. Herein, results obtained from PAT implementations of the second and third types are described for two industrial processes for preparing bulk active pharmaceutical ingredients, demonstrating the benefits in terms of increased process understanding and process control.

  16. Multitask learning improves prediction of cancer drug sensitivity

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    Yuan, Han; Paskov, Ivan; Paskov, Hristo; González, Alvaro J.; Leslie, Christina S.

    2016-01-01

    Precision oncology seeks to predict the best therapeutic option for individual patients based on the molecular characteristics of their tumors. To assess the preclinical feasibility of drug sensitivity prediction, several studies have measured drug responses for cytotoxic and targeted therapies across large collections of genomically and transcriptomically characterized cancer cell lines and trained predictive models using standard methods like elastic net regression. Here we use existing drug response data sets to demonstrate that multitask learning across drugs strongly improves the accuracy and interpretability of drug prediction models. Our method uses trace norm regularization with a highly efficient ADMM (alternating direction method of multipliers) optimization algorithm that readily scales to large data sets. We anticipate that our approach will enhance efforts to exploit growing drug response compendia in order to advance personalized therapy. PMID:27550087

  17. Improved Candidate Drug Mining for Alzheimer’s Disease

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    Yu-Huei Cheng

    2014-01-01

    Full Text Available Alzheimer's disease (AD is the main cause of dementia for older people. Although several antidementia drugs such as donepezil, rivastigmine, galantamine, and memantine have been developed, the effectiveness of AD drug therapy is still far from satisfactory. Recently, the single nucleotide polymorphisms (SNPs have been chosen as one of the personalized medicine markers. Many pharmacogenomics databases have been developed to provide comprehensive information by associating SNPs with drug responses, disease incidence, and genes that are critical in choosing personalized therapy. However, we found that some information from different sets of pharmacogenomics databases is not sufficient and this may limit the potential functions for pharmacogenomics. To address this problem, we used approximate string matching method and data mining approach to improve the searching of pharmacogenomics database. After computation, we can successfully identify more genes linked to AD and AD-related drugs than previous online searching. These improvements may help to improve the pharmacogenomics of AD for personalized medicine.

  18. Improved nanoparticles preparation and drug release for liver targeted delivery

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    Qiao Weili

    2009-05-01

    Full Text Available "nTargeted delivery of drugs and proteins to liver can be achieved via asialoglycoprotein receptor, which can recognize and combine the galactose- and N-acetygalatosamine-terminated glycoproteins. Glycosyl is usually conjugated with drugs directly to fabricate prodrugs or with nanoparticles encapsulated drugs via forming covalent bonds, while the covalent bonds may lead to some shortages for drug release. Therefore, we have a hypothesis that we can prepare nanoparticles for efficient targeting by glycosylation using galactosylated poly (L-glutamic acid (Gal-PLGA as a carrier to entrap the model drugs in nanoparticles core physically rather than forming covalent drug conjugation. The means of incorporation of drug in nanoparticles may improve drug release to maintain its activity, raise its therapeutic index and diminish the adverse effect. Based on previous researches, it is achievable to obtain nanoparticles that we hypothesize to prepare. Due to their nanometer-size and galactosyl, the nanoparticles may be a potential delivery system for passive and active targeting to liver parenchymal cells for therapy of hepatitis and liver cancer.

  19. Improving drug delivery to solid tumors: priming the tumor microenvironment.

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    Khawar, Iftikhar Ali; Kim, Jung Ho; Kuh, Hyo-Jeong

    2015-03-10

    Malignant transformation and growth of the tumor mass tend to induce changes in the surrounding microenvironment. Abnormality of the tumor microenvironment provides a driving force leading not only to tumor progression, including invasion and metastasis, but also to acquisition of drug resistance, including pharmacokinetic (drug delivery-related) and pharmacodynamic (sensitivity-related) resistance. Drug delivery systems exploiting the enhanced permeability and retention (EPR) effect and active targeting moieties were expected to be able to cope with delivery-related drug resistance. However, recent evidence supports a considerable barrier role of tumors via various mechanisms, which results in imperfect or inefficient EPR and/or targeting effect. The components of the tumor microenvironment such as abnormal tumor vascular system, deregulated composition of the extracellular matrix, and interstitial hypertension (elevated interstitial fluid pressure) collectively or cooperatively hinder the drug distribution, which is prerequisite to the efficacy of nanoparticles and small-molecule drugs used in cancer medicine. Hence, the abnormal tumor microenvironment has recently been suggested to be a promising target for the improvement of drug delivery to improve therapeutic efficacy. Strategies to modulate the abnormal tumor microenvironment, referred to here as "solid tumor priming" (vascular normalization and/or solid stress alleviation leading to improvement in blood perfusion and convective molecular movement), have shown promising results in the enhancement of drug delivery and anticancer efficacy. These strategies may provide a novel avenue for the development of new chemotherapeutics and combination chemotherapeutic regimens as well as reassessment of previously ineffective agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. The Drug Facts Box: Improving the communication of prescription drug information

    Science.gov (United States)

    Schwartz, Lisa M.; Woloshin, Steven

    2013-01-01

    Communication about prescription drugs ought to be a paragon of public science communication. Unfortunately, it is not. Consumers see $4 billion of direct-to-consumer advertising annually, which typically fails to present data about how well drugs work. The professional label—the Food and Drug Administration's (FDA) mechanism to get physicians information needed for appropriate prescribing—may also fail to present benefit data. FDA labeling guidance, in fact, suggests that industry omit benefit data for new drugs in an existing class and for drugs approved on the basis of unfamiliar outcomes (such as depression rating scales). The medical literature is also problematic: there is selective reporting of favorable trials, favorable outcomes within trials, and “spinning” unfavorable results to maximize benefit and minimize harm. In contrast, publicly available FDA reviews always include the phase 3 trial data on benefit and harm, which are the basis of drug approval. However, these reviews are practically inaccessible: lengthy, poorly organized, and weakly summarized. To improve accessibility, we developed the Drug Facts Box: a one-page summary of benefit and harm data for each indication of a drug. A series of studies—including national randomized trials—demonstrates that most consumers understand the Drug Facts Box and that it improves decision-making. Despite calls from their own Risk Communication Advisory Committee and Congress (in the Affordable Care Act) to consider implementing boxes, the FDA announced it needs at least 3–5 y more to make a decision. Given its potential public health impact, physicians and the public should not have to wait that long for better drug information. PMID:23942130

  1. Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

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    Giovanni Sotgiu

    2015-03-01

    Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

  2. An Improved Automated Setup for Solubility Determination of Drugs

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    Ahmad Ghanbari 1, Yashar Sarbaz, Vahid Jouyban-Gharamaleki, Karim Jouyban-Gharamaleki, Jafar Soleymani, Abolghasem Jouyban

    2016-09-01

    Full Text Available Background: Solubility of a drug/drug candidate is an essential information in the pharmaceutical area. Classical solubility determination method used in the laboratories are expensive and time-consuming. Attempts were made to provide an automated solubility determination setup based on a laser monitoring technique. Methods: In a previously developed setup, drug powder was added to a given quantity of the solvent which made some troubles in practical applications. The present work reports another setup which adds solvent to a given mass of the drug. The validity of the measured solubilities is checked by comparing the measured solubilities of acetaminophen at two temperatures in water and ethanol mixtures with the corresponding data from the literature. Results: The results reveal that the improved setup could overcome the limitations of the previously developed setup and could be used for drug solubility determination. Conclusion: The improved setup overcomes the troubles made in the previous setup and could be used in generating large amount of solubility data to be used in the pharmaceutical industry.

  3. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

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    Stefano Salmaso

    2013-01-01

    Full Text Available Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.

  4. Improved drug therapy: triangulating phenomics with genomics and metabolomics

    Science.gov (United States)

    2014-01-01

    Embracing the complexity of biological systems has a greater likelihood to improve prediction of clinical drug response. Here we discuss limitations of a singular focus on genomics, epigenomics, proteomics, transcriptomics, metabolomics, or phenomics—highlighting the strengths and weaknesses of each individual technique. In contrast, ‘systems biology’ is proposed to allow clinicians and scientists to extract benefits from each technique, while limiting associated weaknesses by supplementing with other techniques when appropriate. Perfect predictive modeling is not possible, whereas modeling of intertwined phenomic responses using genomic stratification with metabolomic modifications may greatly improve predictive values for drug therapy. We thus propose a novel-integrated approach to personalized medicine that begins with phenomic data, is stratified by genomics, and ultimately refined by metabolomic pathway data. Whereas perfect prediction of efficacy and safety of drug therapy is not possible, improvements can be achieved by embracing the complexity of the biological system. Starting with phenomics, the combination of linking metabolomics to identify common biologic pathways and then stratifying by genomic architecture, might increase predictive values. This systems biology approach has the potential, in specific subsets of patients, to avoid drug therapy that will be either ineffective or unsafe. PMID:25181945

  5. A Cooperative Model to Improve Hospital Equipments and Drugs Management

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    Baffo, Ilaria; Confessore, Giuseppe; Liotta, Giacomo; Stecca, Giuseppe

    The cost of services provided by public and private healthcare systems is nowadays becoming critical. This work tackles the criticalities of hospital equipments and drugs management by emphasizing its implications on the whole healthcare system efficiency. The work presents a multi-agent based model for decisional cooperation in order to address the problem of integration of departments, wards and personnel for improving equipments, and drugs management. The proposed model faces the challenge of (i) gaining the benefits deriving from successful collaborative models already used in industrial systems and (ii) transferring the most appropriate industrial management practices to healthcare systems.

  6. Improving reporting of adverse drug reactions: Systematic review

    Directory of Open Access Journals (Sweden)

    Mariam Molokhia

    2009-05-01

    Full Text Available Mariam Molokhia1, Shivani Tanna2, Derek Bell31Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK; 2Department of Primary Care and Social Medicine, Imperial College, London, UK; 3Division of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UKBackground: Adverse drug reactions (ADRs are a significant cause of morbidity and mortality, with many being identified post-marketing. Improvement in current ADR reporting, including utility of underused or innovative methods, is crucial to improve patient safety and public health.Objectives: To evaluate methods to improve ADR reporting via a systematic literature review.Methods: Data sources were Medline, Embase, Cochrane Library and National Library for health searches on ADR reporting (January 1997 to August 2007 including cross-referenced articles. Twenty-four out of 260 eligible studies were identified and critically assessed. Studies were grouped as follows: i spontaneous reporting (11; ii medical chart/note review (2; iii patient interviews/questionnaires (3; and iv combination methods including computer-assisted methods (8.Results: Using computerized monitoring systems (CMS to generate signals associated with changes in laboratory results with other methods can improve ADR reporting. Educational interventions combined with reminders and/or prescription card reports can improve hospitalbased ADR reporting, and showed short to medium term improvement.Conclusions: The use of electronic health data combined with other methods for ADR reporting can improve efficiency and accuracy for detecting ADRs and can be extended to other health care settings. Although methods with educational intervention appear to be effective, few studies have reviewed long-term effects to assess if the improvements can be sustained. Keywords: adverse drug reaction, reporting, ADR

  7. Strategies to improve intracellular drug delivery by targeted liposomes

    NARCIS (Netherlands)

    Fretz, M.M.

    2007-01-01

    Biotechnological advances increased the number of novel macromolecular drugs and new drug targets. The latter are mostly found intracellular. Unfortunately, most of the new macromolecular drugs rely on drug delivery tools for their intracellular delivery because their unfavourable physicochemical pr

  8. Deploying continuous improvement across the drug discovery value chain.

    Science.gov (United States)

    Walker, Stephen M; Davies, Barry J

    2011-06-01

    In addressing the challenges facing pharmaceutical R&D one question is frequently asked: how can continuous improvement (CI), delivered through a Lean Sigma approach, be applied in a research environment to deliver overall benefit? We show that taking a value chain approach to improvement projects in a discovery research organization, initially focusing on the drug discovery project delivery level (i.e. middle layer of the value chain), provides the foundation for an effective CI programme. The adaptation of Lean Sigma principles and methodology, combined with the tenacity and creativity of scientists, enabled the delivery of significant improvements in challenging areas, including target selection, project decision making and the compound design-make-test-analyse (DMTA) cycle. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Adaptive Programming Improves Outcomes in Drug Court: An Experimental Trial.

    Science.gov (United States)

    Marlowe, Douglas B; Festinger, David S; Dugosh, Karen L; Benasutti, Kathleen M; Fox, Gloria; Croft, Jason R

    2012-04-01

    Prior studies in Drug Courts reported improved outcomes when participants were matched to schedules of judicial status hearings based on their criminological risk level. The current experiment determined whether incremental efficacy could be gained by periodically adjusting the schedule of status hearings and clinical case-management sessions in response to participants' ensuing performance in the program. The adjustments were made pursuant to a priori criteria specified in an adaptive algorithm. Results confirmed that participants in the full adaptive condition (n = 62) were more than twice as likely as those assigned to baseline-matching only (n = 63) to be drug-abstinent during the first 18 weeks of the program; however, graduation rates and the average time to case resolution were not significantly different. The positive effects of the adaptive program appear to have stemmed from holding noncompliant participants more accountable for meeting their attendance obligations in the program. Directions for future research and practice implications are discussed.

  10. The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCd-dependent inhibition of the AKT pathway

    OpenAIRE

    Assad Kahn, Suzana; Lima Costa, Silvia; Gholamin, Sharareh; Nitta, Ryan T.; Dubois, Gustavo Luiz; Fève, Marie; Zeniou, Maria; Cerqueira Coelho, Paulo Lucas; El-Habr, Elias; Cadusseau, Josette; Varlet, Pascale; Mitra, Siddharta S.; Devaux, Bertrand; Kilhoffer, Marie-Claude; Cheshier, Samuel H

    2016-01-01

    Published online; International audience; A variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an a1-and a2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblasto...

  11. Encapsulation of poorly water-soluble drugs into organic nanotubes for improving drug dissolution.

    Science.gov (United States)

    Moribe, Kunikazu; Makishima, Takashi; Higashi, Kenjirou; Liu, Nan; Limwikrant, Waree; Ding, Wuxiao; Masuda, Mitsutoshi; Shimizu, Toshimi; Yamamoto, Keiji

    2014-07-20

    Hydrocortisone (HC), a poorly water-soluble drug, was encapsulated within organic nanotubes (ONTs), which were formed via the self-assembly of N-{12-[(2-α,β-d-glucopyranosyl) carbamoyl]dodecanyl}-glycylglycylglycine acid. The stability of the ONTs was evaluated in ten organic solvents, of differing polarities, by field emission transmission electron microscopy. The ONTs maintained their stable tubular structure in the highly polar solvents, such as ethanol and acetone. Furthermore, solution-state (1)H-NMR spectroscopy confirmed that they were practically insoluble in acetone at 25°C (0.015 mg/mL). HC-loaded ONTs were prepared by solvent evaporation using acetone. A sample with a 3/7 weight ratio of HC/ONT was analyzed by powder X-ray diffraction, which confirmed the presence of a halo pattern and the absence of any crystalline HC peak. HC peak broadening, observed by solid-state (13)C-NMR measurements of the evaporated sample, indicated the absence of HC crystals. These results indicated that HC was successfully encapsulated in ONT as an amorphous state. Improvements of the HC dissolution rate were clearly observed in aqueous media at both pH 1.2 and 6.8, probably due to HC amorphization in the ONTs. Phenytoin, another poorly water-soluble drug, also showed significant dissolution improvement upon ONT encapsulation. Therefore, ONTs can serve as an alternative pharmaceutical excipient to enhance the bioavailability of poorly water-soluble drugs.

  12. Using improved serial blood sampling method of mice to study pharmacokinetics and drug-drug interaction.

    Science.gov (United States)

    Watanabe, Ayahisa; Watari, Ryosuke; Ogawa, Keiko; Shimizu, Ryosuke; Tanaka, Yukari; Takai, Nozomi; Nezasa, Ken-ichi; Yamaguchi, Yoshitaka

    2015-03-01

    In pharmacokinetic evaluation of mice, using serial sampling methods rather than a terminal blood sampling method could reduce the number of animals needed and lead to more reliable data by excluding individual differences. In addition, using serial sampling methods can be valuable for evaluation of the drug-drug interaction (DDI) potential of drug candidates. In this study, we established an improved method for serially sampling the blood from one mouse by only one incision of the lateral tail vein, and investigated whether our method could be adapted to pharmacokinetic and DDI studies. After intravenous and oral administration of ibuprofen and fexofenadine (BCS class II and III), the plasma concentration and pharmacokinetic parameters were evaluated by our method and a terminal blood sampling method, with the result that both methods gave comparable results (ibuprofen: 63.8 ± 4.0% and 64.4%, fexofenadine: 6.5 ± 0.7% and 7.9%, respectively, in bioavailability). In addition, our method could be adapted to DDI study for cytochrome P450 and organic anion transporting polypeptide inhibition. These results demonstrate that our method can be useful for pharmacokinetic evaluation from the perspective of reliable data acquisition as well as easy handling and low stress to mice and improve the quality of pharmacokinetic and DDI studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements.

    Science.gov (United States)

    Mincarone, Pierpaolo; Leo, Carlo Giacomo; Sabina, Saverio; Sarriá-Santamera, Antonio; Taruscio, Domenica; Serrano-Aguilar, Pedro Guillermo; Kanavos, Panos

    2017-01-01

    The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the "regulatory capture" effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases. © 2017 S. Karger AG, Basel.

  14. 78 FR 8446 - Center for Drug Evaluation and Research; Prescription Drug Labeling Improvement and Enhancement...

    Science.gov (United States)

    2013-02-06

    ... prescription drug products and reducing the likelihood of medication errors. FDA implemented standardized... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 201, 314, and 601 Center for Drug Evaluation... and Information AGENCY: Food and Drug Administration, HHS. ACTION: Notification of an...

  15. Drug Does Not Improve Set of Cardiovascular Outcomes for Diastolic Heart Failure

    Science.gov (United States)

    ... not improve set of cardiovascular outcomes for diastolic heart failure NIH-supported study finds drug does appear to reduce hospitalizations for diastolic heart failure. A drug that blocks the action of a ...

  16. Physicochemical Properties of Solid Phospholipid Particles as a Drug Delivery Platform for Improving Oral Absorption of Poorly Soluble Drugs.

    Science.gov (United States)

    Kawakami, Kohsaku; Miyazaki, Aoi; Fukushima, Mayuko; Sato, Keiko; Yamamura, Yuko; Mohri, Kohta; Sakuma, Shinji

    2017-01-01

    A novel drug delivery platform, mesoporous phospholipid particle (MPP), is introduced. Its physicochemical properties and ability as a carrier for enhancing oral absorption of poorly soluble drugs are discussed. MPP was prepared through freeze-drying a cyclohexane/t-butyl alcohol solution of phosphatidylcholine. Its basic properties were revealed using scanning electron microscopy, x-ray diffraction, thermal analysis, hygroscopicity measurement, and so on. Fenofibrate was loaded to MPP as a poorly soluble model drug, and effect of MPP on the oral absorption behavior was observed. MPP is spherical in shape with a diameter typically in the range of 10-15 μm and a wide surface area that exceeds 10 m(2)/g. It has a bilayer structure that may accommodate hydrophobic drugs in the acyl chain region. When fenofibrate was loaded in MPP as a model drug, it existed partially in a crystalline state and improvement in the dissolution behavior was achieved in the presence of a surfactant, because of the formation of mixed micelles composed of phospholipids and surfactants in the dissolution media. MPP greatly improved the oral absorption of fenofibrate compared to that of the crystalline drug and its efficacy was almost equivalent to that of an amorphous drug dispersion. MPP is a promising option for improving the oral absorption of poorly soluble drugs based on the novel mechanism of dissolution improvement.

  17. Nanomedicine for improved efficacy of tuberculosis drugs – Pharmacokinetic importance

    CSIR Research Space (South Africa)

    Hayeshi, R

    2012-10-01

    Full Text Available Efficacy of Tuberculosis Drugs ? Pharmacokinetic importance Emerging Researcher Symposium Dr. Rose Hayeshi 10 October 2012 Outline ? Challenges in TB treatment ? Nanomedicine as proposed solution ? Results ? Conclusions ? CSIR 2012 Slide 2... ? 1 x 106 cfu/lung 3 x 103 cfu/spleen Effects of the Nanodrug on Mycobacaterium tuberculosis replication ? Nanodrug once a week vs conventional drug daily ? Treatment with nanoencapsulated TB drugs once a week, comparable to daily treatment...

  18. Systems pharmacology modeling: an approach to improving drug safety.

    Science.gov (United States)

    Bai, Jane P F; Fontana, Robert J; Price, Nathan D; Sangar, Vineet

    2014-01-01

    Advances in systems biology in conjunction with the expansion in knowledge of drug effects and diseases present an unprecedented opportunity to extend traditional pharmacokinetic and pharmacodynamic modeling/analysis to conduct systems pharmacology modeling. Many drugs that cause liver injury and myopathies have been studied extensively. Mitochondrion-centric systems pharmacology modeling is important since drug toxicity across a large number of pharmacological classes converges to mitochondrial injury and death. Approaches to systems pharmacology modeling of drug effects need to consider drug exposure, organelle and cellular phenotypes across all key cell types of human organs, organ-specific clinical biomarkers/phenotypes, gene-drug interaction and immune responses. Systems modeling approaches, that leverage the knowledge base constructed from curating a selected list of drugs across a wide range of pharmacological classes, will provide a critically needed blueprint for making informed decisions to reduce the rate of attrition for drugs in development and increase the number of drugs with an acceptable benefit/risk ratio.

  19. Improving Drugs Administration Safety in Pediatric Resuscitation Using Mobile Technology.

    Science.gov (United States)

    Hagberg, Hamdi; Siebert, Johan; Gervaix, Alain; Daehne, Peter; Lovis, Christian; Manzano, Sergio; Ehrler, Frederic

    2016-01-01

    The fast preparation of drugs during pediatric resuscitation is of utmost importance. The influence of the patient's weight on the drug doses requires to perform complex calculations and is a source of errors. A technological solution could be a real help in avoiding these kinds of mistakes. Relying on a user centered approach we have developed an application supporting drug preparation. It has been tested in simulations with predefined scenario. The developed tool consists of a screen displaying a list of drug that can be administered. When the user select a drug, the instructions regarding its preparation are displayed with all dosage precisely calculated. The tool has demonstrated a significant reduction of errors associated to administration, a speeding up the overall process and has been well received by the nurses.

  20. Integrating translational neuroscience to improve drug abuse treatment for adolescents.

    Science.gov (United States)

    Boyce, Cheryl Anne; Lynne-Landsman, Sarah D

    2013-06-01

    Adolescence is an exciting and challenging period of maturation, rapid brain development, and developmental changes in neurobiological, neurocognitive, and neurobehavioral processes. Although behavioral therapies available for adolescent substance abuse have increased, effectiveness research in this area lags considerably behind that of clinical research on treatment for drug-abusing adults. Behavioral treatment approaches show significant promise for treating drug-abusing adolescents, but many have not incorporated innovations in neuroscience on brain development, cognitive processes, and neuroimaging. Linking developmental neuroscience with behavioral treatments can create novel drug abuse interventions and increase the effectiveness of existing interventions for substance-abusing adolescents. Contemporary research on brain development, cognition, and neuroscience is ripe for translation to inform developmentally sensitive drug abuse treatments for adolescents. Neuroscientists and interventionists are challenged to build mutual collaborations for integration of neuroscience and drug abuse treatment for adolescents.

  1. SELF EMULSIFYING DRUG DELIVERY SYSTEM: A CONVENTIONAL AND ALTERNATIVE APPPROACH TO IMPROVE ORAL BIOAVAILABILITY OF LIPOPHILIC DRUGS

    Directory of Open Access Journals (Sweden)

    Desai Tushar R

    2010-12-01

    Full Text Available Out of newly discovered drugs most of the drugs are found to be lipophilic and out of which up to 40 % of pharmacologically active new molecules failed to reach to market only due to little or no water solubility; a serious challenge for the successful development and commercialization of new drugs in the pharmaceutica lindustry. Therefore various formulation strategies have been investigated to improve the solubility and the rate of dissolut ion to enhance the oral bioavailability of lipophilic drugs. Amongst various approach self emulsifying drug delivery system has gained more attention due to enhanced oral bio-availability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s toward specific absorption window in GIT, and protection of drug(s from the hostile environment in gut. The present review discussed the mechanisam of self emulsification, composition, formulation approaches, different techniques, evaluation, factors affecting SEDDS, advantages, draw backs, applications and future trends in SEDDS.

  2. Improving Drug Sensitivity Prediction Using Different Types of Data.

    Science.gov (United States)

    Hejase, H A; Chan, C

    2015-02-01

    The algorithms and models used to address the two subchallenges that are part of the NCI-DREAM (Dialogue for Reverse Engineering Assessments and Methods) Drug Sensitivity Prediction Challenge (2012) are presented. In subchallenge 1, a bidirectional search algorithm is introduced and optimized using an ensemble scheme and a nonlinear support vector machine (SVM) is then applied to predict the effects of the drug compounds on breast cancer cell lines. In subchallenge 2, a weighted Euclidean distance method is introduced to predict and rank the drug combinations from the most to the least effective in reducing the viability of a diffuse large B-cell lymphoma (DLBCL) cell line.

  3. Improving Drug Sensitivity Prediction Using Different Types of Data

    OpenAIRE

    Hejase, HA; Chan, C.

    2015-01-01

    The algorithms and models used to address the two subchallenges that are part of the NCI-DREAM (Dialogue for Reverse Engineering Assessments and Methods) Drug Sensitivity Prediction Challenge (2012) are presented. In subchallenge 1, a bidirectional search algorithm is introduced and optimized using an ensemble scheme and a nonlinear support vector machine (SVM) is then applied to predict the effects of the drug compounds on breast cancer cell lines. In subchallenge 2, a weighted Euclidean dis...

  4. Improving Detection of Arrhythmia Drug-Drug Interactions in Pharmacovigilance Data through the Implementation of Similarity-Based Modeling.

    Directory of Open Access Journals (Sweden)

    Santiago Vilar

    Full Text Available Identification of Drug-Drug Interactions (DDIs is a significant challenge during drug development and clinical practice. DDIs are responsible for many adverse drug effects (ADEs, decreasing patient quality of life and causing higher care expenses. DDIs are not systematically evaluated in pre-clinical or clinical trials and so the FDA U. S. Food and Drug Administration relies on post-marketing surveillance to monitor patient safety. However, existing pharmacovigilance algorithms show poor performance for detecting DDIs exhibiting prohibitively high false positive rates. Alternatively, methods based on chemical structure and pharmacological similarity have shown promise in adverse drug event detection. We hypothesize that the use of chemical biology data in a post hoc analysis of pharmacovigilance results will significantly improve the detection of dangerous interactions. Our model integrates a reference standard of DDIs known to cause arrhythmias with drug similarity data. To compare similarity between drugs we used chemical structure (both 2D and 3D molecular structure, adverse drug side effects, chemogenomic targets, drug indication classes, and known drug-drug interactions. We evaluated the method on external reference standards. Our results showed an enhancement of sensitivity, specificity and precision in different top positions with the use of similarity measures to rank the candidates extracted from pharmacovigilance data. For the top 100 DDI candidates, similarity-based modeling yielded close to twofold precision enhancement compared to the proportional reporting ratio (PRR. Moreover, the method helps in the DDI decision making through the identification of the DDI in the reference standard that generated the candidate.

  5. Development of a salt drug with improved solubility: Ethionamide nitrate

    Science.gov (United States)

    Diniz, Luan F.; Carvalho, Paulo S.; de Melo, Cristiane C.; Ellena, Javier

    2017-06-01

    To avoid drug resistance, an adequate tuberculosis treatment should include not only a first-line drug but also at least one second-line drug such as, for example, Ethionamide (ETH). However, the dissolution rate and oral absorption of ETH is highly limited by its low aqueous solubility. Considering that a salt is in general more soluble than its parent compound, herein we depicted a new supramolecular modification of ETH, an Ethionamide nitrate salt (ETHNO3). This salt is the first ETH structure that has been crystallized with four independent ionic pairs (ETH+NO3-) in the asymmetric unit. In addition to the structural study, the salt formation was also identified on the FT-IR and FT-Raman spectra. The thermal behavior of ETHNO3 was also investigated here together with its solubility profile in three dissolution media (purified water, pH 4.0 and 7.0).

  6. Therapeutic drug monitoring : how to improve drug dosage and patient safety in tuberculosis treatment

    NARCIS (Netherlands)

    Sotgiu, Giovanni; Alffenaar, Jan-Willem C.; Centis, Rosella; D'Ambrosio, Lia; Spanevello, Antonio; Piana, Andrea; Migliori, Giovanni Battista

    2015-01-01

    In this article we describe the key role of tuberculosis (TB) treatment, the challenges (mainly the emergence of drug resistance), and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contrib

  7. Drugs and diagnostic innovations to improve global health.

    Science.gov (United States)

    Peeling, Rosanna W; Nwaka, Solomon

    2011-09-01

    Infectious diseases remain the major cause of morbidity and mortality in the developing world. Affordable effective drugs and diagnostics are critical for patient management and disease control but the development of new drugs and diagnostics is too slow to keep up with the emergence and spread of infectious diseases around the world. Innovative collaborative research and development involving disease endemic countries and developed countries are urgently needed to accelerate progress along the path from discovery to product adoption. These emerging approaches and the need for increased investment in human and financial resources to support them are discussed.

  8. Coupling of drug containing liposomes to microbubbles improves ultrasound triggered drug delivery in mice.

    Science.gov (United States)

    Cool, Steven K; Geers, Bart; Roels, Stefan; Stremersch, Stephan; Vanderperren, Katrien; Saunders, Jimmy H; De Smedt, Stefaan C; Demeester, Joseph; Sanders, Niek N

    2013-12-28

    Local extravasation and triggered drug delivery by use of ultrasound and microbubbles is a promising strategy to target drugs to their sites of action. In the past we have developed drug loaded microbubbles by coupling drug containing liposomes to the surface of microbubbles. Until now the advantages of this drug loading strategy have only been demonstrated in vitro. Therefore, in this paper, microbubbles with indocyanine green (ICG) containing liposomes at their surface or a mixture of ICG-liposomes and microbubbles was injected intravenously in mice. Immediately after injection the left hind leg was exposed to 1 MHz ultrasound and the ICG deposition was monitored 1, 4 and 7 days post-treatment by in vivo fluorescence imaging. In mice that received the ICG-liposome loaded microbubbles the local ICG deposition was, at each time point, about 2-fold higher than in mice that received ICG-liposomes mixed with microbubbles. We also showed that the perforations in the blood vessels allow the passage of ICG-liposomes up to 5h after microbubble and ultrasound treatment. An increase in tissue temperature to 41°C was observed in all ultrasound treated mice. However, ultrasound tissue heating was excluded to cause the local ICG deposition. We concluded that coupling of drug containing liposomes to microbubbles may increase ultrasound mediated drug delivery in vivo.

  9. [Preparation of two poor water soluble drugs - nanoporous ZnO solid dispersions and the mechanism of drug dissolution improvement].

    Science.gov (United States)

    Gao, Bei; Sun, Chang-shan; Zhi, Zhuang-zhi; Wang, Yan; Chang, Di; Wang, Si-ling; Jiang, Tong-ying

    2011-11-01

    Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.

  10. Targeting Plasmodium Metabolism to Improve Antimalarial Drug Design.

    Science.gov (United States)

    Avitia-Domínguez, Claudia; Sierra-Campos, Erick; Betancourt-Conde, Irene; Aguirre-Raudry, Miriam; Vázquez-Raygoza, Alejandra; Luevano-De la Cruz, Artemisa; Favela-Candia, Alejandro; Sarabia-Sanchez, Marie; Ríos-Soto, Lluvia; Méndez-Hernández, Edna; Cisneros-Martínez, Jorge; Palacio-Gastélum, Marcelo Gómez; Valdez-Solana, Mónica; Hernández-Rivera, Jessica; De Lira-Sánchez, Jaime; Campos-Almazán, Mara; Téllez-Valencia, Alfredo

    2016-01-01

    Malaria is one of the main infectious diseases in tropical developing countries and represents high morbidity and mortality rates nowadays. The principal etiological agent P. falciparum is transmitted through the bite of the female Anopheles mosquito. The issue has escalated due to the emergence of resistant strains to most of the antimalarials used for the treatment including Chloroquine, Sulfadoxine-Pyrimethamine, and recently Artemisinin derivatives, which has led to diminished effectiveness and by consequence increased the severity of epidemic outbreaks. Due to the lack of effective compounds to treat these drug-resistant strains, the discovery or development of novel anti-malaria drugs is important. In this context, one strategy has been to find inhibitors of enzymes, which play an important role for parasite survival. Today, promising results have been obtained in this regard, involving the entire P. falciparum metabolism. These inhibitors could serve as leads in the search of a new chemotherapy against malaria. This review focuses on the achievements in recent years with regard to inhibition of enzymes used as targets for drug design against malaria.

  11. Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability

    Directory of Open Access Journals (Sweden)

    Prakash Khadka

    2014-12-01

    Full Text Available Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral administration. The particle technology involves several approaches from the conventional size reduction processes to the newer, novel particle technologies that modify the solubility properties of the drugs and produce solid, powdered form of the drugs that are readily soluble in water and can be easily formulated into various dosage forms. This review highlights the solid particle technologies available for improving solubility, dissolution and bioavailability of drugs with poor aqueous solubility.

  12. Did the diabetes check improve drug adherence of Dutch patients with diabetes?: an intervention study.

    NARCIS (Netherlands)

    Hendriks, M.; Vervloet, M.; Dijk, L. van

    2005-01-01

    Background: Poor adherence to treatment of chronic diseases is a worldwide problem. Medicines are often part of therapy and appropriate drug use is important in optimizing health care outcomes. Pharmacies can improve drug adherence by providing information and assistance to their patients. Several i

  13. Application of gold nanoparticles for improved drug efficiency

    Science.gov (United States)

    Shittu, K. O.; Bankole, M. T.; Abdulkareem, A. S.; Abubakre, O. K.; Ubaka, A. U.

    2017-09-01

    Due to increasing resistance of microorganisms towards current antibiotics, there is a need for new or enhanced antibiotics. Nanotechnology is a technology that enhances the use of gold nanoparticles (AuNP) in area of medical applications, especially as a drug carrier for targeted drug delivery. In this research, AuNPs was synthesized using biological method via bioreduction of Piper guineense aqueous leaf extract on tetra gold chloride, characterized using UV-Vis spectrophometer, DLS, TEM/EDS and FTIR. The synthesized AuNPs was covalently functionalized with polyethylene glycol and encapsulated with Lincomycin and in vitro dissolution methods was used to evaluate the potential performance of the formulated nanodrug. The nanodrug has highest release efficiency at the 9th minutes (23.4 mg ml-1 for 40 °C) and (29.5 mg ml-1 for 60 °C) compared with the non-nanodrug. The antibacterial potential of the nanodrug was seen on the gram-positive bacteria of Staphylococcus aureus and Streptococcus pyogenes with highest inhibitions of 18 mm (at 40 °C) and 16 mm (at 60 °C) for S. aureus, and 16 mm for S. pyogenes (both at 40 °C and 60 °C). The bacteria growth inhibition continued and lasted for 15 min, while that of non-nanodrug lasted for 9 min with lesser growth inhibition compared to the formulated nanodrug. This work shows that the presence of the AuNPs increased the release efficiency of lincomycin even at a lower concentration and also bacteria growth inhibition thereby suggesting the effectiveness of the nanodrug formulation.

  14. 75 FR 996 - Medicare Prescription Drug, Improvement, and Modernization Act of 2003 Section 1013: Request for...

    Science.gov (United States)

    2010-01-07

    ... committees. ] Healthcare, industry, and professional organizations. Academic researchers (including, but not... HUMAN SERVICES Agency for Healthcare Research and Quality Medicare Prescription Drug, Improvement, and... AGENCY: Agency for Healthcare Research and Quality (AHRQ), DHHS. ACTION: Notice of invitation to...

  15. Probiotic B420 and prebiotic polydextrose improve efficacy of antidiabetic drugs in mice

    National Research Council Canada - National Science Library

    Stenman, Lotta K; Waget, Aurélie; Garret, Céline; Briand, François; Burcelin, Rémy; Sulpice, Thierry; Lahtinen, Sampo

    2015-01-01

    Gut microbiota is now known to control glucose metabolism. Previous studies have shown that probiotics and prebiotics may improve glucose metabolism, but their effects have not been studied in combination with drug therapy...

  16. Student nurses need more than maths to improve their drug calculating skills.

    Science.gov (United States)

    Wright, Kerri

    2007-05-01

    Nurses need to be able to calculate accurate drug calculations in order to safely administer drugs to their patients (NMC, 2002). Studies have shown however that nurses do not always have the necessary skills to calculate accurate drug dosages and are potentially administering incorrect dosages of drugs to their patients (Hutton, M. 1998. Nursing Mathematics: the importance of application. Nursing Standard 13(11), 35-38; Kapborg, I. 1994. Calculation and administration of drug dosage by Swedish nurses, Student Nurses and Physicians. International Journal for Quality in Health Care 6(4), 389-395; O'Shea, E. 1999. Factors contributing to medication errors: a literature review. Journal of Advanced Nursing 8, 496-504; Wilson, A. 2003. Nurses maths: researching a practical approach. Nursing Standard 17(47), 33-36). The literature indicates that in order to improve drug calculations strategies need to focus on both the mathematical skills and conceptual skills of student nurses so they can interpret clinical data into drug calculations to be solved. A study was undertaken to investigate the effectiveness of implementing several strategies which focussed on developing the mathematical and conceptual skills of student nurses to improve their drug calculation skills. The study found that implementing a range of strategies which addressed these two developmental areas significantly improved the drug calculation skills of nurses. The study also indicates that a range of strategies has the potential ensuring that the skills taught are retained by the student nurses. Although the strategies significantly improved the drug calculation skills of student nurses, the fact that only 2 students were able to achieve 100% in their drug calculation test indicates a need for further research into this area.

  17. Targeting Receptors, Transporters and Site of Absorption to Improve Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    J.H. Hamman

    2007-01-01

    Full Text Available Although the oral route of drug administration is the most acceptable way of self-medication with a high degree of patient compliance, the intestinal absorption of many drugs is severely hampered by different biological barriers. These barriers comprise of biochemical and physical components. The biochemical barrier includes enzymatic degradation in the gastrointestinal lumen, brush border and in the cytoplasm of the epithelial cells as well as efflux transporters that pump drug molecules from inside the epithelial cell back to the gastrointestinal lumen. The physical barrier consists of the epithelial cell membranes, tight junctions and mucus layer. Different strategies have been applied to improve the absorption of drugs after oral administration, which range from chemical modification of drug molecules and formulation technologies to the targeting of receptors, transporters and specialized cells such as the gut-associated lymphoid tissues. This review focuses specifically on the targeting of receptor-mediated endocytosis, transporters and the absorption-site as methods of optimizing intestinal drug absorption. Intestinal epithelial cells express several nutrient transporters that can be targeted by modifying the drug molecule in such a way that it is recognized as a substrate. Receptor-mediated endocytosis is a transport mechanism that can be targeted for instance by linking a receptor substrate to the drug molecule of interest. Many formulation strategies exist for enhancing drug absorption of which one is to deliver drugs at a specific site in the gastrointestinal tract where optimum drug absorption takes place.

  18. Targeting receptors, transporters and site of absorption to improve oral drug delivery.

    Science.gov (United States)

    Hamman, J H; Demana, P H; Olivier, E I

    2007-01-01

    Although the oral route of drug administration is the most acceptable way of self-medication with a high degree of patient compliance, the intestinal absorption of many drugs is severely hampered by different biological barriers. These barriers comprise of biochemical and physical components. The biochemical barrier includes enzymatic degradation in the gastrointestinal lumen, brush border and in the cytoplasm of the epithelial cells as well as efflux transporters that pump drug molecules from inside the epithelial cell back to the gastrointestinal lumen. The physical barrier consists of the epithelial cell membranes, tight junctions and mucus layer. Different strategies have been applied to improve the absorption of drugs after oral administration, which range from chemical modification of drug molecules and formulation technologies to the targeting of receptors, transporters and specialized cells such as the gut-associated lymphoid tissues. This review focuses specifically on the targeting of receptor-mediated endocytosis, transporters and the absorption-site as methods of optimizing intestinal drug absorption. Intestinal epithelial cells express several nutrient transporters that can be targeted by modifying the drug molecule in such a way that it is recognized as a substrate. Receptor-mediated endocytosis is a transport mechanism that can be targeted for instance by linking a receptor substrate to the drug molecule of interest. Many formulation strategies exist for enhancing drug absorption of which one is to deliver drugs at a specific site in the gastrointestinal tract where optimum drug absorption takes place.

  19. [The importance of clinical data management in improvement of drug evaluation].

    Science.gov (United States)

    Huang, Qin; Wang, Jun

    2015-11-01

    Although the importance of clinical data is drawing more attention in drug development in China, the clinical data management is not good enough in the clinical trials right now. With the development of internet and progress of information technology, especially with the setup of the state innovation strategy for drug development, it is necessary and urgent to improve the clinical data quality. Good data quality is the primary basis of technical evaluation of drug at the marketing authorization. So Center for Drug Evaluation of CFDA has made some endeavors to enhance data management in the clinical trials in recent years. This article is focused on these aspects of data managment.

  20. Pharmaceutical pricing: a review of proposals to improve access and affordability of prescription drugs.

    Science.gov (United States)

    Tironi, Paula

    2010-01-01

    This article discusses how pharmaceutical innovation achieves remarkable improvements in human health but a significant portion of the U.S. population cannot afford prescription drugs. The author examines ways that patent protection, generics, supply chain complexity, and the cost of innovation and promotion affect access and affordability. The author then looks at the influences of marketing strategies and industry trends such as the patent cliff and pipeline for new drugs, innovations in biotechnology and genomics, comparative effectiveness analysis, and payor and employer strategies on drug prices. An analysis of reform proposals in the context of industry trends suggests that promoting generic drug use and availability through education, prohibiting authorized generics, and restricting the practice of developing follow-on drugs and discontinuing the original formulations upon patent expiration could improve access and affordability most quickly and significantly.

  1. Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation Mechanism: An Update.

    Science.gov (United States)

    Yang, Meiyan; Gong, Wei; Wang, Yuli; Shan, Li; Li, Ying; Gao, Chunsheng

    2016-01-01

    The formulation development for poorly soluble drugs still remains a challenge. Supersaturating drug delivery systems (SDDS) or drug delivery systems based on supersaturating provide a promising way to improve the oral bioavailability of poorly water-soluble drugs. In supersaturable formulations, drug concentration exceeds the equilibrium solubility when exposed to gastrointestinal fluids, and the supersaturation state is maintained long enough to be absorbed, resulting in compromised bioavailability. In this article, the mechanism of generating and maintaining supersaturation and the evaluation methods of supersaturation assays are discussed. Recent advances in different drug delivery systems based on supersaturating are the focus and are discussed in detail.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  2. Systems biology-embedded target validation: improving efficacy in drug discovery.

    Science.gov (United States)

    Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

    2014-01-01

    The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment.

  3. Clinical Pharmacology of Alpha-1 Blockers Improving Drug-profile through Novel Formulations.

    Science.gov (United States)

    Nerurkar, Rajan P; Ved, Jignesh K

    2014-09-01

    Clinical pharmacology is an essential consideration in chronic therapies, and may play a significant role in modifying the pharmacological characteristics of drug formulations. Improvement in drug formulations may ensure their safe and effective use over a period of time. This has been particularly observed with α-1 adrenergic blockers in hypertension management. Advancements in formulations like prazosin GITS, have resulted in improvement in tolerability profile and smoother, more effective blood pressure control, which reasonably translate into improvement in patient compliance and better clinical outcomes.

  4. Selective speciation improves efficacy and lowers toxicity of platinum anticancer and vanadium antidiabetic drugs.

    Science.gov (United States)

    Doucette, Kaitlin A; Hassell, Kelly N; Crans, Debbie C

    2016-12-01

    Improving efficacy and lowering resistance to metal-based drugs can be addressed by consideration of the coordination complex speciation and key reactions important to vanadium antidiabetic drugs or platinum anticancer drugs under biological conditions. The methods of analyses vary depending on the specific metal ion chemistry. The vanadium compounds interconvert readily, whereas the reactions of the platinum compounds are much slower and thus much easier to study. However, the vanadium species are readily differentiated due to vanadium complexes differing in color. For both vanadium and platinum systems, understanding the processes as the compounds, Lipoplatin and Satraplatin, enter cells is needed to better combat the disease; there are many cellular metabolites, which may affect processing and thus the efficacy of the drugs. Examples of two formulations of platinum compounds illustrate how changing the chemistry of the platinum will result in less toxic and better tolerated drugs. The consequence of the much lower toxicity of the drug, can be readily realized because cisplatin administration requires hospital stay whereas Lipoplatin can be done in an outpatient manner. Similarly, the properties of Satraplatin allow for development of an oral drug. These forms of platinum demonstrate that the direct consequence of more selective speciation is lower side effects and cheaper administration of the anticancer agent. Therefore we urge that as the community goes forward in development of new drugs, control of speciation chemistry will be considered as one of the key strategies in the future development of anticancer drugs.

  5. Subsidizing the distribution channel: Donor funding to improve the availability of malaria drugs

    OpenAIRE

    Taylor, TA; W. Xiao

    2014-01-01

    ©2014 INFORMS. In countries that bear the heaviest burden of malaria, most patients seek medicine for the disease in the private sector. Because the availability and affordability of recommended malaria drugs provided by the private-sector distribution channel is poor, donors (e.g., the Global Fund) are devoting substantial resources to fund subsidies that encourage the channel to improve access to these drugs. A key question for a donor is whether it should subsidize the purchases and/or the...

  6. Improved prediction of drug-target interactions using regularized least squares integrating with kernel fusion technique

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Ming; Wang, Yanli, E-mail: ywang@ncbi.nlm.nih.gov; Bryant, Stephen H., E-mail: bryant@ncbi.nlm.nih.gov

    2016-02-25

    Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision–recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein-coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross-validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as polypharmacology, and may help to accelerate drug discovery by identifying novel drug targets. - Graphical abstract: Flowchart of the proposed RLS-KF algorithm for drug-target interaction predictions. - Highlights: • A nonlinear kernel fusion algorithm is proposed to perform drug-target interaction predictions. • Performance can further be improved by using the recalculated kernel. • Top predictions can be validated by experimental data.

  7. Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids

    Science.gov (United States)

    Simovic, Spomenka; Barnes, Timothy J.; Tan, Angel; Prestidge, Clive A.

    2012-02-01

    Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

  8. Hybrid systems based on "drug - in cyclodextrin - in nanoclays" for improving oxaprozin dissolution properties.

    Science.gov (United States)

    Mura, Paola; Maestrelli, Francesca; Aguzzi, Carola; Viseras, César

    2016-07-25

    A combined approach based on drug complexation with cyclodextrins, and complex entrapment in nanoclays has been investigated, to join in a single delivery system the benefits of these carriers and potentiate their ability to improve the dissolution properties of oxaprozin (OXA), a poorly water-soluble anti-inflammatory drug. Based on previous studies, randomly methylated ß-cyclodextrin (RAMEB) was chosen as the most effective cyclodextrin for OXA complexation. Adsorption equilibrium studies performed on three different clays (sepiolite, attapulgite, bentonite) allowed selection of sepiolite (SV) for its greater adsorption power towards OXA. DSC and XRPD studies indicated drug amorphization in both binary OXA-RAMEB coground and OXA-SV cofused products, due to its complexation or very fine dispersion in the clay structure, respectively. The drug amorphous state was maintained also in the ternary OXA-RAMEB-SV cofused system. Dissolution studies evidenced a clear synergistic effect of RAMEB complexation and clay nanoencapsulation in improving the OXA dissolution properties, with an almost 100% increase in percent dissolved and dissolution efficiency compared to the OXA-RAMEB coground system. Therefore, the proposed combined approach represents an interesting tool for improving the therapeutic effectiveness of poorly soluble drugs, and reducing the CD amount necessary for obtaining the desired drug solubility and dissolution rate increase. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Modified-chitosan nanoparticles: Novel drug delivery systems improve oral bioavailability of doxorubicin.

    Science.gov (United States)

    Khdair, Ayman; Hamad, Islam; Alkhatib, Hatim; Bustanji, Yasser; Mohammad, Mohammad; Tayem, Rabab; Aiedeh, Khaled

    2016-10-10

    The efficacy of most anticancer drugs is highly limited in vivo due mainly to poor pharmacokinetics behavior including poor bioavailability after extravascular administration. We have developed novel chitosan-modified polymeric nanoparticles for oral as well as i.v. administration. Nanoparticles were developed utilizing the double emulsion solvent evaporation technique for sustained delivery of various anticancer drugs. Chitosan diacetate (CDA) and chitosan triacetate (CTA) polymers were previously modified in our laboratory and used as novel matrix. Nanoparticles, loaded with various anticancer drugs, were characterized for particle size using dynamic light scattering as well as transmission electron microscopy and net surface charge using dynamic light scattering. Particles size was below 100nm in diameter and zeta potential ranged - (25-30). Encapsulation efficiency of anticancer drugs varied considerably and was dependent on the physicochemical characteristics of the encapsulated drug. However, chitosan triacetate nanoparticles showed relatively higher encapsulation efficiency than chitosan diacetate nanoparticles. In vitro release of encapsulated drugs was sustained over a period of 14days. Nanoparticles enhanced cellular accumulation of encapsulated drugs, compared to the free drugs, in vitro in MCF-7 and Caco-II tumor cell lines. In conclusion, diacetate and triacetate chitosan are novel polymers that can be used to formulate nanoparticles which efficiently encapsulated anticancer drugs, and sustained the release and enhanced tumor cellular uptake of these drugs. Further, chitosan triacetate nanoparticles enhanced oral bioavailability of doxorubicin. CDA and CTA nanoparticles can be used to efficiently deliver anticancer drugs and improve their in vivo profile. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

    Science.gov (United States)

    Meanwell, Nicholas A

    2011-09-19

    The development of small molecule drug candidates from the discovery phase to a marketed product continues to be a challenging enterprise with very low success rates that have fostered the perception of poor productivity by the pharmaceutical industry. Although there have been significant advances in preclinical profiling that have improved compound triaging and altered the underlying reasons for compound attrition, the failure rates have not appreciably changed. As part of an effort to more deeply understand the reasons for candidate failure, there has been considerable interest in analyzing the physicochemical properties of marketed drugs for the purpose of comparing with drugs in discovery and development as a means capturing recent trends in drug design. The scenario that has emerged is one in which contemporary drug discovery is thought to be focused too heavily on advancing candidates with profiles that are most easily satisfied by molecules with increased molecular weight and higher overall lipophilicity. The preponderance of molecules expressing these properties is frequently a function of increased aromatic ring count when compared with that of the drugs launched in the latter half of the 20th century and may reflect a preoccupation with maximizing target affinity rather than taking a more holistic approach to drug design. These attributes not only present challenges for formulation and absorption but also may influence the manifestation of toxicity during development. By providing some definition around the optimal physicochemical properties associated with marketed drugs, guidelines for drug design have been developed that are based largely on calculated parameters and which may readily be applied by medicinal chemists as an aid to understanding candidate quality. The physicochemical properties of a molecule that are consistent with the potential for good oral absorption were initially defined by Lipinski, with additional insights allowing further

  11. Improving anticancer drug development begins with cell culture: misinformation perpetrated by the misuse of cytotoxicity assays.

    Science.gov (United States)

    Eastman, Alan

    2017-01-31

    The high failure rate of anticancer drug discovery and development has consumed billions of dollars annually. While many explanations have been provided, I believe that misinformation arising from inappropriate cell-based screens has been completely over-looked. Most cell culture experiments are irrelevant to how drugs are subsequently administered to patients. Usually, drug development focuses on growth inhibition rather than cell killing. Drugs are selected based on continuous incubation of cells, then frequently administered to the patient as a bolus. Target identification and validation is often performed by gene suppression that inevitably mimics continuous target inhibition. Drug concentrations in vitro frequently far exceed in vivo concentrations. Studies of drug synergy are performed at sub-optimal concentrations. And the focus on a limited number of cell lines can misrepresent the potential efficacy in a patient population. The intent of this review is to encourage more appropriate experimental design and data interpretation, and to improve drug development in the area of cell-based assays. Application of these principles should greatly enhance the successful translation of novel drugs to the patient.

  12. Can Functional Magnetic Resonance Imaging Improve Success Rates in CNS Drug Discovery?

    Science.gov (United States)

    Borsook, David; Hargreaves, Richard; Becerra, Lino

    2011-01-01

    Introduction The bar for developing new treatments for CNS disease is getting progressively higher and fewer novel mechanisms are being discovered, validated and developed. The high costs of drug discovery necessitate early decisions to ensure the best molecules and hypotheses are tested in expensive late stage clinical trials. The discovery of brain imaging biomarkers that can bridge preclinical to clinical CNS drug discovery and provide a ‘language of translation’ affords the opportunity to improve the objectivity of decision-making. Areas Covered This review discusses the benefits, challenges and potential issues of using a science based biomarker strategy to change the paradigm of CNS drug development and increase success rates in the discovery of new medicines. The authors have summarized PubMed and Google Scholar based publication searches to identify recent advances in functional, structural and chemical brain imaging and have discussed how these techniques may be useful in defining CNS disease state and drug effects during drug development. Expert opinion The use of novel brain imaging biomarkers holds the bold promise of making neuroscience drug discovery smarter by increasing the objectivity of decision making thereby improving the probability of success of identifying useful drugs to treat CNS diseases. Functional imaging holds the promise to: (1) define pharmacodynamic markers as an index of target engagement (2) improve translational medicine paradigms to predict efficacy; (3) evaluate CNS efficacy and safety based on brain activation; (4) determine brain activity drug dose-response relationships and (5) provide an objective evaluation of symptom response and disease modification. PMID:21765857

  13. ANTITUBERCULOSIS DRUG DOSAGE FORMS: RANGE, KEY BENEFITS AND PROSPECTS OF TECHNOLOGICAL IMPROVEMENT

    Directory of Open Access Journals (Sweden)

    M. E. Kim

    2016-01-01

    Full Text Available Interest to research in the development of new formulations of antituberculosis drugs due to the high incidence of tuberculosis in the Republic of Kazakhstan and the Russian Federation nowadays, including with acquired drug resistance. The reason for the development of acquired drug resistance is to interrupt the treatment of patients is the high toxicity of antituberculosis drugs. The improving the efficiency of antituberculosis therapy remains one of the most pressing.The aim this study was to review the dosage forms of antituberculosis drugs currently used and the ways to improve them.Methods. The study was conducted on the basis of scientific analysis (eLibrary database, PubMed, Cyberleninca, patent (kzpatents, reference (Klifar, Drugs register and technical literature.Results. It was revealed that the antituberculosis drugs are available in the form of tablets, capsules, granules for oral use and injection solutions. The advantages and disadvantages of oral dosage forms of antituberculosis drugs: tablets, capsules, granules, syrups, suspensions are described. The importance of the development and implementation in practice of pediatric formulations of antituberculosis drugs is mentioned. The state of current research inhaled formulations for the treatment of tuberculosis is described. The prospects of directional inhalation exposure by immobilization of antituberculosis drugs in liposomes, niosomes, nanocapsules, micelles, micro- and nanoparticles are mentioned. The prospect of the rectal formulations use is described. The increase in interest in the molecular encapsulation of medicinal substances with cyclodextrins in connection with the possibility of increasing the bioavailability of active ingredients, reduce the harmful effects on the gastrointestinal tract, extension, elimination of interaction of incompatible components in combination preparations, the protection of unstable substances is

  14. Mesoporous silica-based dosage forms improve release characteristics of poorly soluble drugs: case example fenofibrate.

    Science.gov (United States)

    Dressman, Jennifer B; Herbert, Elisabeth; Wieber, Alena; Birk, Gudrun; Saal, Christoph; Lubda, Dieter

    2016-05-01

    Mesoporous silica-based dosage forms offer the potential for improving the absorption of poorly soluble drugs after oral administration. In this investigation, fenofibrate was used as a model drug to study the ability of monomodal ('PSP A') and bimodal ('PSP B') porous silica to improve release by a 'spring' effect in in vitro biorelevant dissolution tests. Also investigated was the addition of various polymers to provide a 'parachute' effect, that is, to keep the drug in solution after its release. Loading fenofibrate onto PSP A or PSP B porous silica substantially improved the dissolution profile of fenofibrate under fasted state conditions compared with both pure drug and the marketed product, TriCor® 145 mg. Adding a polymer such as hydroxypropyl methylcellulose acetate succinate, polyvinylpyrrolidone or copovidon (HPMCAS, PVP or PVPVA) sustains the higher release of fenofibrate from the PSP A silica, resulting in a combination 'spring and parachute' effect - loading the drug onto the silica causes a 'spring' effect while the polymer enhances the spring effect (HPMCAS, PVP) and adds a sustaining 'parachute'. Interestingly, a silica to polymer ratio of 4:1 w/w appears to have an optimal effect for fenofibrate (HPMCAS, PVP). Dissolution results under conditions simulating the fasted state in the small intestine with the PSP A or the PSP B silica with HPMCAS added in a 4:1 w/w ratio show very substantial improvement over the marketed, nanosized product (TriCor® 145 mg). Further experiments to determine whether the highly positive effects on fenofibrate release observed with the silica prototypes investigated to date can be translated to further poorly soluble drugs and to what extent they translate into improved in-vivo performance are warranted. © 2015 Royal Pharmaceutical Society.

  15. Novel therapeutic modalities and drug delivery in pancreatic cancer – an ongoing search for improved efficacy

    Directory of Open Access Journals (Sweden)

    Yuqing Zhang

    2012-12-01

    Full Text Available Pancreatic cancer is an incredibly challenging disease due to its high rates of resistance to traditional chemotherapy and radiotherapy. There has been little improvement in the prognosis of pancreatic cancer cases in the past decades, highlighting the crucial need for more effective therapeutic approaches. Erlotinib, an EGFR inhibitor, and gemcitabine, a nucleoside analog, are currently used in combination for chemotherapy treatment, but new developments in drug delivery systems using liposomes and nanoparticles may be promising new modalities for management of the disease. In addition to standard chemotherapeutic drugs, these delivery systems can be utilized to deliver therapeutic agents such as siRNA, oncolytic viruses, small molecule inhibitors, antibodies, and suicide genes. Further work is required to elucidate how ligands and antibodies could be used to enhance the targeted delivery of drugs, thus increasing specificity, improving stability, and reducing the effect of the drugs on healthy tissue. Despite significant preclinical data, there are currently very few clinical trials involving pancreatic cancer targeted drug delivery. This article summarizes current developments in targeted pancreatic cancer drug delivery, focusing on delivery systems, targets, and therapeutic agents.

  16. An educational intervention on drug use in nursing homes improves health outcomes resource utilization and reduces inappropriate drug prescription.

    Science.gov (United States)

    García-Gollarte, Fermín; Baleriola-Júlvez, José; Ferrero-López, Isabel; Cuenllas-Díaz, Álvaro; Cruz-Jentoft, Alfonso J

    2014-12-01

    Inappropriate drug prescription is a common problem in people living in nursing homes and is linked to adverse health outcomes. This study assessed the effect of an educational intervention directed to nursing home physicians in reducing inappropriate prescription and improving health outcomes and resource utilization. Prospective, randomized, multicenter study. A private organization of nursing homes in Spain. Sixty nursing home physicians caring for approximately 3900 nursing home residents in 37 centers were randomized to receive an educational intervention (30) or as a control group (30). 10 hours educational program, followed by on demand support by phone. Outcomes were assessed in 1018 randomly selected nursing home residents. Appropriateness of drug use [measured by the Screening Tool of Older Persons Prescriptions (STOPP) and Screening Tool to Alert Doctors to Right Treatment (START) criteria], incidence of selected geriatric syndromes (falls, delirium) and health resource utilization (visits to physicians and nursing homes, visits to the emergency room, days of hospitalization) were recorded for 3 months before the intervention started and 3 months after the intervention finished. O total of 716 residents finished the study (344 cared for by the intervention group physicians, 372 cared for by control physicians). Mean age was 84.4 ± 12.7 years; 73% were women. The mean number of inappropriate drugs (STOPP criteria) was higher at the end of the study in the control than in the intervention group (1.29 ± 1.56 vs 0.81 ± 1.13), as was the number of residents on 6 or more drugs (76.5% vs.67.0%), using antipsychotics (9.1% vs 3.2%) or duplicate medications (32.5% vs 9.2%). The number of fallers increased in the control group (from 19.3% to 28%) and did not significantly change in the intervention group (from 25.3% to 23.9%); the number of residents with delirium increased in the control group (from 3.8% to 9.1%) and decreased in the intervention group (from 6

  17. Improved Therapeutic Efficacy in Bone and Joint Disorders by Targeted Drug Delivery to Bone.

    Science.gov (United States)

    Takahashi, Tatsuo

    2016-01-01

     Site-specific drug delivery to bone is considered achievable using acidic amino acid (L-Asp or L-Glu) homopeptides known as acidic oligopeptides. We found that fluorescence-labeled acidic oligopeptides containing six or more residues bound strongly to hydroxyapatite, which is a major component of bone, and were selectively delivered to and retained in bone after systemic administration. We explored the applicability of this result for drug delivery by conjugation of estradiol and levofloxacin with an L-Asp hexapeptide. We also similarly tagged enzymes (tissue-nonspecific alkaline phosphatase, β-glucuronidase, and N-acetylgalactosamine-6-sulfate sulfatase) and decoy receptors (endogenous secretory receptor for advanced glycation end products and etanercept) to assess whether these would improve therapeutic efficacy. The L-Asp hexapeptide-tagged drugs, including enzymes and decoy receptors, were efficiently delivered to bone in comparison with the untagged drugs. An in vivo experiment confirmed the efficacy of L-Asp hexapeptide-tagged drugs on bone and joint disorders, although there was some loss of bioactivity of estradiol and levofloxacin in vitro, suggesting that the acidic hexapeptide was partly removed by hydrolysis in the body after delivery to bone. It was expected that the ester linkage to the hexapeptide would be susceptible to hydrolysis in situ, releasing the drug from the acidic oligopeptide. These results support the usefulness of acidic oligopeptides as bone-targeting carriers for therapeutic agents. We present some pharmacokinetic and pharmacological properties of the L-Asp hexapeptide-tagged drugs.

  18. Improving the quality of adverse drug reaction reporting by 4th-year medical students.

    Science.gov (United States)

    Rosebraugh, Curtis J; Tsong, Yi; Zhou, Feng; Chen, Min; Mackey, Ann Corken; Flowers, Charlene; Toyer, Denise; Flockhart, David A; Honig, Peter K

    2003-03-01

    Evaluate whether a 15-minute lecture intervention will improve adverse drug reaction reporting quality on standard MedWatch forms. Seventy-eight 4th-year medical students were randomized to intervention 'Group-A' or non-intervention 'Group-B' on the first day of a required five-day clinical pharmacology rotation. Group-A participants attended a 15-minute lecture on completing a MedWatch form with quality information considered by the Food and Drug Administration as critical to adequate adverse drug reaction reporting. Group-B participants did not attend this lecture. Both groups then watched a standardized patient interview of a recognizable adverse drug reaction and completed MedWatch forms. Four Safety Evaluators from the Food and Drug Administration (FDA) rated student responses in a blinded fashion for the primary efficacy variable of Overall Impression and six informational domins using a standardized data quality analysis form that was developed within the Office of Postmarketing Drug Risk Assessment of the FDA. Seventy-eight MedWatch forms were evaluated (Group-A = 40, Group B = 38). Overall MedWatch information quality scores for the intervention group were significantly higher than the non-intervention group (p students. Academic medical centers should consider incorporating adverse drug reaction reporting curriculum into the clinical training of medical students.

  19. Overview and appraisal of the current concept and technologies for improvement of sublingual drug delivery.

    Science.gov (United States)

    Wang, Zhijun; Chow, Moses Ss

    2014-07-01

    Sublingual drug delivery is capable of achieving high bioavailability by avoiding first-pass liver extraction and enzymatic degradation in the gastrointestinal tract, as well as achieving rapid onset of effect. Thus, this route of administration can offer attractive therapeutic advantages for certain drugs as a convenient substitute for parenteral administration and has been applied successfully to a number of therapeutic conditions, especially urgent cardiovascular conditions and acute severe pain control. However, due to inherent limitations such as small sublingual mucosa area for absorption, primarily passive mechanism of transport, short residence time, and potential local irritation, a relatively small number of sublingual products have been successfully developed to date. In this Review, key concepts and technologies for potential improvement of sublingual drug delivery are reviewed. The optimal application of these concepts and technologies, together with clinical need for non-parenteral delivery, will hopefully broaden the development of sublingual drug delivery in the future.

  20. Role of Solvents in Improvement of Dissolution Rate of Drugs: Crystal Habit and Crystal Agglomeration

    Directory of Open Access Journals (Sweden)

    Maryam Maghsoodi

    2015-03-01

    Full Text Available Crystallization is often used for manufacturing drug substances. Advances of crystallization have achieved control over drug identity and purity, but control over the physical form remains poor. This review discusses the influence of solvents used in crystallization process on crystal habit and agglomeration of crystals with potential implication for dissolution. According to literature it has been known that habit modification of crystals by use of proper solvents may enhance the dissolution properties by changing the size, number and the nature of crystal faces exposed to the dissolution medium. Also, the faster dissolution rate of drug from the agglomerates of crystals compared with the single crystals may be related to porous structure of the agglomerates and consequently their better wettability. It is concluded from this review that in-depth understanding of role of the solvents in crystallization process can be applied to engineering of crystal habit or crystal agglomeration, and predictably dissolution improvement in poorly soluble drugs.

  1. Information Technology-Based Interventions to Improve Drug-Drug Interaction Outcomes: A Systematic Review on Features and Effects.

    Science.gov (United States)

    Nabovati, Ehsan; Vakili-Arki, Hasan; Taherzadeh, Zhila; Saberi, Mohammad Reza; Medlock, Stephanie; Abu-Hanna, Ameen; Eslami, Saeid

    2017-01-01

    The purpose of this systematic review was to identify features and effects of information technology (IT)-based interventions on outcomes related to drug-drug interactions (DDI outcomes). A literature search was conducted in Medline, EMBASE, and the Cochrane Library for published English-language studies. Studies were included if a main outcome was related to DDIs, the intervention involved an IT-based system, and the study design was experimental or observational with controls. Study characteristics, including features and effects of IT-based interventions, were extracted. Nineteen studies comprising five randomized controlled trials (RCT), five non-randomized controlled trials (NRCT) and nine observational studies with controls (OWC) were included. Sixty-four percent of prescriber-directed interventions, and all non-prescriber interventions, were effective. Each of the following characteristics corresponded to groups of studies of which a majority were effective: automatic provision of recommendations within the providers' workflow, intervention at the time of decision-making, integration into other systems, and requiring the reason for not following the recommendations. Only two studies measured clinical outcomes: an RCT that showed no significant improvement and an OWC that showed improvement, but did not statistically assess the effect. Most studies that measured surrogate outcomes (e.g. potential DDIs) and other outcomes (e.g. adherence to alerts) showed improvements. IT-based interventions improve surrogate clinical outcomes and adherence to DDI alerts. However, there is lack of robust evidence about their effectiveness on clinical outcomes. It is recommended that researchers consider the identified features of effective interventions in the design of interventions and evaluate the effectiveness on DDI outcomes, particularly clinical outcomes.

  2. The use of nationwide on-line prescription records improves the drug history in hospitalized patients

    DEFF Research Database (Denmark)

    Glintborg, Bente; Poulsen, Henrik E; Dalhoff, Kim P

    2008-01-01

    What is already known about this subject: Structured medication interviews improve the medication history upon hospitalization. Pharmacy records are valid lists of the prescribed medications available to individual patients. In Denmark, treating doctors now have access to their patients' pharmacy...... records through a real-time online electronic database What this study adds: Omission errors are frequent among hospitalized patients despite structured drug interviews and home visits. Pharmacy records may be used to minimize patients' recall bias and improve the medication lists....

  3. The use of nationwide on-line prescription records improves the drug history in hospitalized patients

    DEFF Research Database (Denmark)

    Glintborg, Bente; Poulsen, Henrik E; Dalhoff, Kim P

    2008-01-01

    records through a real-time online electronic database What this study adds: Omission errors are frequent among hospitalized patients despite structured drug interviews and home visits. Pharmacy records may be used to minimize patients' recall bias and improve the medication lists.......What is already known about this subject: Structured medication interviews improve the medication history upon hospitalization. Pharmacy records are valid lists of the prescribed medications available to individual patients. In Denmark, treating doctors now have access to their patients' pharmacy...

  4. A new and improved method for the preparation of drug nanosuspension formulations using acoustic mixing technology.

    Science.gov (United States)

    Leung, Dennis H; Lamberto, David J; Liu, Lina; Kwong, Elizabeth; Nelson, Todd; Rhodes, Timothy; Bak, Annette

    2014-10-01

    Drug discovery and development is a challenging area. During the drug optimization process, available drug compounds often have poor physicochemical and biopharmaceutical properties, making the proper in vivo evaluation of these compounds difficult. To address these challenges, drug nanoparticles of poorly soluble compounds have emerged as a promising formulation approach. Herein, we report on a new drug sparing technology utilizing low shear acoustic mixing to rapidly identify optimized nanosuspension formulations for a wide range of compounds with dramatically improved material and time efficiencies. This approach has several key advantages over typical methods of preparing nanoparticles, including miniaturization of the milling process, the ability to evaluate multiple formulation conditions in a high throughput manner, and direct translation to optimized formulation scale-up for in vivo studies. Furthermore, there are additional benefits obtained with this new approach resulting in nanosuspension formulations with significant stability and physical property enhancements over those obtained using traditional media milling techniques. These advantages make this approach highly suitable for the rapid evaluation of potential drug candidates in the discovery and development space.

  5. Feature Selection in Detection of Adverse Drug Reactions from the Health Improvement Network (THIN Database

    Directory of Open Access Journals (Sweden)

    Yihui Liu

    2015-02-01

    Full Text Available Adverse drug reaction (ADR is widely concerned for public health issue. ADRs are one of most common causes to withdraw some drugs from market. Prescription event monitoring (PEM is an important approach to detect the adverse drug reactions. The main problem to deal with this method is how to automatically extract the medical events or side effects from high-throughput medical events, which are collected from day to day clinical practice. In this study we propose a novel concept of feature matrix to detect the ADRs. Feature matrix, which is extracted from big medical data from The Health Improvement Network (THIN database, is created to characterize the medical events for the patients who take drugs. Feature matrix builds the foundation for the irregular and big medical data. Then feature selection methods are performed on feature matrix to detect the significant features. Finally the ADRs can be located based on the significant features. The experiments are carried out on three drugs: Atorvastatin, Alendronate, and Metoclopramide. Major side effects for each drug are detected and better performance is achieved compared to other computerized methods. The detected ADRs are based on computerized methods, further investigation is needed.

  6. A comparative study on the nanoparticles for improved drug delivery systems.

    Science.gov (United States)

    Mahmoodi, Nosrat O; Ghavidast, Atefeh; Amirmahani, Najmeh

    2016-09-01

    Nanoparticles have attracted considerable recent interest for diverse biomedical applications because of the unique properties of the nanomaterials. It is already known that one of the major advances in the relative application of nanoparticles is the recognition of the steric stabilization which can increase the particle stability in the biological environment and provide the opportunities of the application of nanoparticles in the development of drug delivery systems (DDSs) for achieving drug targeting and controlled drug release. To facilitate their use in such applications, the appropriate design of surface ligands on these nanoparticles is necessary. In view of these, functionalized nanoparticles through surface modification can be utilized to specifically interact with the target molecules on the cell membrane or intracellular ones. This review briefly presents self-assembled nanoparticles with molecules of therapeutic significance with two strategies. The first strategy attempts to improve the placement of the drugs using conjugating the appropriate ligands or adding targeting moieties to the DDS. The second strategy utilizes trigger-controlled drug-release, which restricts drug release at the targeted site to kill cancer cells by externally controlled mechanisms. Among external stimulations, conveniently light has attracted much interest because it, as an orthogonal external stimulus, gives spatiotemporal control of payload release.

  7. Requirement of Family Enterprises of Feed and Veterinary Drugs for Improving Professional Manager Mechanism and Recommendations

    Institute of Scientific and Technical Information of China (English)

    Zhongming; SHEN

    2014-01-01

    In the development of family enterprises of feed and veterinary drugs in China,there are many problems,such as lack of organic integration of human capital and social human capital.This paper introduced development thread of family enterprises of feed and veterinary drugs in China,analyzed theories and practical development requirement for improving professional manager mechanism,and came up with recommendations including establishing proper employing system,incentive and restraint mechanism,corporate culture,and professional manager market.

  8. Improving Protocol Design Feasibility to Drive Drug Development Economics and Performance

    Directory of Open Access Journals (Sweden)

    Kenneth Getz

    2014-05-01

    Full Text Available Protocol design complexity has increased substantially during the past decade and this in turn has adversely impacted drug development economics and performance. This article reviews the results of two major Tufts Center for the Study of Drug Development studies quantifying the direct cost of conducting less essential and unnecessary protocol procedures and of implementing amendments to protocol designs. Indirect costs including personnel time, work load and cycle time delays associated with complex protocol designs are also discussed. The author concludes with an overview of steps that research sponsors are taking to improve protocol design feasibility.

  9. Improvement of drug exposure data in a registration of congenital anomalies. Pilot-study : Pharmacist and mother as sources for drug exposure data during pregnancy

    NARCIS (Netherlands)

    Van den Berg, LTWDJ; Feenstra, N; Sorensen, HT; Cornel, MC

    1999-01-01

    We examined the possibilities of improving the retrospective collection of data an drug use during pregnancy. The European Registration of Congenital Anomalies (EUROCAT) has registered information on maternal drug exposure in the northern Netherlands through a question on the notification form for t

  10. Evaluation of Effectiveness of Integrated Intervention Program in Improving Drug Addicts' Psychological Health1

    Institute of Scientific and Technical Information of China (English)

    YA-QIONG YAN; YONG-YOU LIU; YUE-FENG ZENG; YI-WEI CUI; JI-WEI LEI; ZENG-ZHEN WANG

    2008-01-01

    Objective To investigate the social mental state of drug addicts in a compulsive drug abuse treatment center;evaluate the effectiveness of integrated program for the prevention of abuse relapse and improvement of drug addicts' psychological health.Methods The study subjects were addicts from the Wuhan Compulsive Drug Abuse Treatment Center between October 2003 and June 2004,who satisfied the inclusion criteria.A non-randomized control-intervention study design was adopted.Volunteers willing to take part in intervention were put into the intervention group with their full awareness and willingness to prevent drug abuse relapse.The control group was composed of the addicts who were willing to prevent relapse and to be followed up after their discharge. Results The effectiveness of the integrated intervention program in promoting addicts' psychological health:before the intervention,the scores of Self-Rating Anxiety Scale(SAS),the positive and negative dimensionalities of Simple Coping Style Questionnaire(SCSQ)and Chinese Perceived Stress Scales(CPSS)had no significant differences between the intervention group and the control group.After the intervention,exccpt that the SCSQ's positive dimensionality in the intervention group was significantly higher than that in the control group,other indices in the intervention group were lower.Before and after the intervention.the psychological health level in both the groups was lower than that in the normal population;there were significant differences between addicts and normal subjects in regards with all of the indices above. Conclusion Drug abuse was associated closely with addicts' social mental factors.The integrated intervention program can alleviate anxiety and stress,reduce co-morbid mental disorders and effectively improve their coping style.In conclusion,the program can promote addicts' psychological health significantly.

  11. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  12. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol.

    Science.gov (United States)

    Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed As

    2016-01-01

    Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17-99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of -2.24 to -15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities

  13. Solid Dispersion Approach Improving Dissolution Rate of Stiripentol: a Novel Antiepileptic Drug.

    Science.gov (United States)

    Afifi, Samar

    2015-01-01

    Some drugs have low bioavailability due to their poor aqueous solubility and/or slow dissolution rate in biological fluids. Stiripentol (STP) is a novel anticonvulsant drug that is structurally unrelated to the currently available antiepileptics. It has poor aqueous solubility and its solubility has to be enhanced accordingly. Polyethyleneglycol 6000 (PEG-6000) is commonly utilized as a hydrophilic carrier for poorly water soluble drugs in order to improve their bioavailability. STP and PEG-6000 binary system was obtained by physical mixture, solvent evaporation, co-evaporation and melting methods using different weight ratios. The properties of the prepared binary systems were evaluated using dissolution rate, phase solubility, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) studies. The FTIR spectroscopic studies showed the stability of STP and absence of STP-PEG-6000 interaction. The DSC and SEM studies indicated the amorphous state of STP in its binary systems with PEG-6000. Dissolution profile of STP was significantly improved via complexation with PEG-6000 as compared with the pure drug. The binary system which was prepared using melting method showed the highest dissolution rate. The promising results of the prepared binary systems open the avenue for further oral formulation of STP.

  14. Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Buregyeya, Esther; Rutebemberwa, Elizeus

    2016-01-01

    OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety in the p......OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety......, available antibiotics, knowledge on treatment of pneumonia in children aged antibiotic. RESULTS: A total of 170 registered drug shops were surveyed between August and October 2014. The majority of drug shops, 93.......5% were prescribing antibiotics, especially amoxicillin and trimethoprim-sulfamethoxazole (septrin). The professional qualification of a provider was significantly associated with this practice, p=0.04; where lower cadre staff (nursing assistants and enrolled nurses) overprescribed antibiotics. A third...

  15. [Improvement of intestinal absorption of poorly absorbable drugs by various sugar esters].

    Science.gov (United States)

    Yamamoto, Akira; Katsumi, Hidemasa; Kusamori, Kosuke; Sakane, Toshiyasu

    2014-01-01

    Effects of sucrose fatty acid esters (sugar esters) on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption of CF from the rat small intestine was significantly enhanced in the presence of various sugar esters and a maximal absorption enhancing effect was observed in the presence of 0.5%(w/v) S-1670. The absorption enhancing effect of S-1670 in the small intestine decreased as the molecular weights of drugs increased. Moreover, we evaluated the intestinal membrane damage with or without various sugar esters. These sugar esters (0.5%(w/v)) did not increase the activities of lactate dehydrogenase (LDH), suggesting that these sugar esters did not cause serious membrane damage to the intestinal epithelium. Furthermore, these sugar esters increased membrane fluidity of lipid layers of the intestinal brush border membranes and decreased the transepithelial electrical resistance (TEER) of Caco-2 cells. Therefore, these findings suggested that these sugar esters might improve the intestinal absorption of poorly absorbable drugs via a transcellular and a paracellular pathways.

  16. Improved antimicrobial property and controlled drug release kinetics of silver sulfadiazine loaded ordered mesoporous silica

    Directory of Open Access Journals (Sweden)

    Suman Jangra

    2016-09-01

    Full Text Available The present study deals with the loading of silver sulfadiazine into ordered mesoporous silica material by post-impregnation method and its effect on the in vitro release kinetics and antimicrobial property of the drug. The formulated SBA-15 silica material with rope-like morphology and SBA-15-silver sulfadiazine (SBA-AgSD were characterized by UV–visible spectrophotometer, small and wide-angle powder X-ray diffraction (PXRD, field emission scanning electron microscope (FESEM and high resolution transmission electron microscope (HRTEM. Thermo-gravimetric analysis of SBA-AgSD revealed a high loading amount of 52.87%. Nitrogen adsorption–desorption analysis confirmed the drug entrapment into host material by revealing a reduced surface area (214 m2/g and pore diameter (6.7 nm of the SBA-AgSD. The controlled release of silver sulfadiazine drug from the mesoporous silica to simulated gastric, intestinal and body fluids was evaluated. The Korsmeyer–Peppas model fits the drug release data with the non-Fickian diffusion model and zero order kinetics of SBA-AgSD. The antibacterial performance of the SBA-AgSD was evaluated with respect to Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa. The controlled drug delivery of the SBA-AgSD revealed improved antibacterial activity, thus endorsing its applicability in effective wound dressing.

  17. Doxorubicin-loaded platelets as a smart drug delivery system: An improved therapy for lymphoma

    Science.gov (United States)

    Xu, Peipei; Zuo, Huaqin; Chen, Bing; Wang, Ruju; Ahmed, Arsalan; Hu, Yong; Ouyang, Jian

    2017-01-01

    Chemotherapy is majorly used for the treatment of many cancers, including lymphoma. However, cytotoxic drugs, utilized in chemotherapy, can induce various side effects on normal tissues because of their non-specific distribution in the body. Natural platelets are used as drug carriers because of their biocompatibility and specific targeting to vascular disorders, such as cancer, inflammation, and thrombosis. In this work, doxorubicin (DOX) was loaded in natural platelets for treatment of lymphoma. Results showed that DOX was loaded into platelets with high drug loading and encapsulation efficiency. DOX did not significantly induce morphological and functional changes in platelets. DOX-platelet facilitated intracellular drug accumulation through “tumor cell-induced platelet aggregation” and released DOX into the medium in a pH-controlled manner. This phenomenon reduced the adverse effects and enhanced the therapeutic efficacy. The growth inhibition of lymphoma Raji cells was enhanced, and the cardiotoxicity of DOX was reduced when DOX was loaded in platelets. DOX-platelet improved the anti-tumor activity of DOX by regulating the expression of apoptosis-related genes. Thus, platelets can serve as potential drug carriers to deliver DOX for clinical treatment of lymphoma. PMID:28198453

  18. Improvement of dissolution property of poorly water-soluble drug by supercritical freeze granulation.

    Science.gov (United States)

    Sonoda, Ryoichi; Hara, Yuko; Iwasaki, Tomohiro; Watano, Satoru

    2009-10-01

    The dissolution property of the poorly water-soluble drug, flurbiprofen (FP) was improved by a novel supercritical freeze granulation using supercritical carbon dioxide. Supercritical freeze granulation was defined as a production method of the granulated substances by using the dry ice to generate intentionally for the rapid atomization of the supercritical carbon dioxide to the atmospheric pressure. This process utilized a rapid expansion of supercritical solutions (RESS) process with the mixture of the drug and lactose. In the supercritical freeze granulation, needle-like FP fine particles were obtained which adhered to the surface of lactose particles, which did not dissolve in supercritical carbon dioxide. The number of FP particles that adhered to the surface of particles decreased with an increase in the ratio of lactose added, leading to markedly improve the dissolution rate. This improvement was caused not only by the increase in the specific surface area but also the improvement of the dispersibility of FP in water. It is thus concluded that the supercritical freeze granulation is a useful technique to improve the dissolution property of the poorly water-soluble flurbiprofen.

  19. Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report.

    Science.gov (United States)

    Laes, JoAn R; Williams, David M; Cole, Jon B

    2015-12-01

    The purpose of this study is to describe a case where methylene blue improved hemodynamics in a poisoned patient. This is a single case report where a poisoned patient developed vasodilatory shock following ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple therapies including vasopressors, high-dose insulin, hemodialysis, and 20% intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was administered in the ICU with temporal improvement as measured by pulmonary artery catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h of methylene blue administration, systemic vascular resistance improved (240 dyn s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with maintenance of mean arterial pressure 60 mmHg. Methylene blue may improve hemodynamics in drug-induced vasodilatory shock and should be considered in critically ill patients poisoned with vasodilatory medications refractory to standard therapies.

  20. PPO/PEO modified hollow fiber membranes improved sensitivity of 3D cultured hepatocytes to drug toxicity via suppressing drug adsorption on membranes.

    Science.gov (United States)

    Shen, Chong; Meng, Qin; He, Wenjuan; Wang, Qichen; Zhang, Guoliang

    2014-11-01

    The three dimensional (3D) cell culture in polymer-based micro system has become a useful tool for in vitro drug discovery. Among those polymers, polysulfone hollow fiber membrane (PSf HFM) is commonly used to create a microenvironment for cells. However, the target drug may adsorb on the polymeric surface, and this elicits negative impacts on cell exposure due to the reduced effective drug concentration in culture medium. In order to reduce the drug adsorption, PSf membrane were modified with hydrophilic Pluronic (PEO-b-PPO-b-PEO) copolymers, L121, P123 and F127 (PEO contents increase from 10%, 30% to 70%), by physical adsorption. As a result, the hydrophilicity of HFMs increased at an order of PSfF127>P123>L121 HFMs. The three modified membrane all showed significant resistance to adsorption of acid/neutral drugs. More importantly, the adsorption of base drugs were largely reduced to an average value of 11% on the L121 HFM. The improved resistance to drug adsorption could be attributed to the synergy of hydrophobic/neutrally charged PPO and hydrophilic PEO. The L121 HFM was further assessed by evaluating the drug hepatotoxicity in 3D culture of hepatocytes. The base drugs, clozapine and doxorubicin, showed more sensitive hepatotoxicity on hepatocytes in L121 HFM than in PSf HFM, while the acid drug, salicylic acid, showed the similar hepatotoxicity to hepatocytes in both HFMs. Our finding suggests that PSf HFM modified by PEO-b-PPO-b-PEO copolymers can efficiently resist the drug adsorption onto polymer membrane, and consequently improve the accuracy and sensitivity of in vitro hepatotoxic drug screening.

  1. Improved therapeutic entities derived from known generics as an unexplored source of innovative drug products.

    Science.gov (United States)

    Stegemann, Sven; Klebovich, Imre; Antal, István; Blume, Henning H; Magyar, Kálmán; Németh, György; Paál, Tamás L; Stumptner, Willibald; Thaler, György; Van de Putte, Armand; Shah, Vinod P

    2011-11-20

    With a New Drug Application (NDA) innovative drug therapies are reaching the market in a specific dosage form for one or more clinically proven indications of which after expiration of the patent or the data exclusivity copies are launched using Abbreviated New Drug Applications (ANDA). Advanced therapies that emerged from launched molecules during their product life-cycle have gained considerable attention as clinical practice provides evidence for additional therapeutic values, patient centric delivery systems show improved therapeutic outcomes or emerging technologies offer efficiency gains in manufacturing or access to emerging markets. The USA and European regulatory framework has set reasonable regulations in place for these "Supergenerics" or "hybrid" applications. While these regulations are relatively recent the pharmaceutical industry is just starting to use this route for their product development and life-cycle management. From a clinical perspective the potential for advanced product development have been demonstrated. Yet, there is still a lag of common understanding between the different stakeholders regarding the development, application process and commercial incentive in developing enhanced therapeutic entities based on existing drug products for the market.

  2. AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution.

    Science.gov (United States)

    Balogh, Attila; Farkas, Balázs; Verreck, Geert; Mensch, Jürgen; Borbás, Enikő; Nagy, Brigitta; Marosi, György; Nagy, Zsombor Kristóf

    2016-05-30

    Alternating current electrospinning (ACES) capable to reach multiple times higher specific productivities than widely used direct current electrospinning (DCES) was investigated and compared with DCES to prepare drug-loaded formulations based on one of the most widespread polymeric matrix used for commercialized pharmaceutical solid dispersions, hydroxypropylmethylcellulose 2910 (HPMC). In order to improve the insufficient spinnability of HPMC (both with ACES and DCES) polyethylene oxide (PEO) as secondary polymer with intense ACES activity was introduced into the electrospinning solution. Different grades of this polymer used at as low concentrations in the fibers as 0.1% or less enabled the production of high quality HPMC-based fibrous mats without altering its physicochemical properties remarkably. Increasing concentrations of higher molecular weight PEOs led to the thickening of fibers from submicronic diameters to several microns of thickness. ACES fibers loaded with the poorly water-soluble model drug spironolactone were several times thinner than drug-loaded fibers prepared with DCES in spite of the higher feeding rates applied. The amorphous HPMC-based fibers with large surface area enhanced the dissolution of spironolactone significantly, the presence of small amounts of PEO did not affect the dissolution rate. The presented results confirm the diverse applicability of ACES, a novel technique to prepare fibrous drug delivery systems.

  3. Transglycosylated stevia and hesperidin as pharmaceutical excipients: dramatic improvement in drug dissolution and bioavailability.

    Science.gov (United States)

    Uchiyama, Hiromasa; Tozuka, Yuichi; Imono, Masaaki; Takeuchi, Hirofumi

    2010-10-01

    The capability of transglycosylated materials, α-glycosyltransferase-treated stevia (Stevia-G) and α-glycosyl hesperidin (Hsp-G), to enhance the bioavailability of poorly water-soluble drugs was investigated. Spray-dried particles (SDPs) of drug/transglycosylated material, such as, flurbiprofen (FP)/Stevia-G, probucol (PRO)/Stevia-G, FP/Hsp-G, and PRO/Hsp-G were prepared. All SDPs showed pronounced improvement in both dissolution rate and apparent drug solubility. The amount of dissolved PRO was significantly improved to that of untreated PRO crystals when prepared as SDPs of PRO/Stevia-G or PRO/Hsp-G. There was no cytotoxicity to Caco-2 cells at levels of 10% Stevia-G or Hsp-G solution. Values for the area under the plasma concentration-time curve (AUC) of untreated PRO, SDPs of PRO/Hsp-G and PRO/Stevia-G after oral administration to rats were 4.94±2.06, 26.08±4.52 and 48.79±9.97μgh/mL, respectively. Interestingly, AUC values in cases of the FP system were in the order of untreated FPStevia-GStevia-G, a newly investigated material for this purpose, was found to have good potential for use as a pharmaceutical excipient.

  4. Modulation of Intercellular Junction by Utilization of Cadherin Peptides as an Effort to Improve Drug Delivery

    Directory of Open Access Journals (Sweden)

    Usman Sumo Friend Tambunan

    2004-04-01

    Full Text Available Rapid advances in combinatorial chemistry and molecular biology has influenced the discovery of many proteins, peptides and peptidomimetics as potential therapeutic agents. Unfortunately, the practical application of these potential drugs is often restricted by the difficulties of delivering them to target site(s due to the presence of biological barriers. Recently, a new method to improve the drug delivery, that is by modulating the intercellular junction, has been evaluated. Modulation of intercellular junction could be achieved by modulating the proteins which play important role in establishing the intercellular junction, one of which is cadherin. In the present work we have demonstrated the ability of several cadherin peptides, i.e. Ac-LFSHAVSSNG-NH2 (HAV-10, Ac-SHAVSS-NH2 (HAV-6, Ac-QGADTPPVGV-NH2 (ADT-10, and Ac-ADTPPV-NH2 (ADT-6 to modulate the intercellular junction of MDCK (Madin Darby Canine Kidney cells, this finding is a contribution to the establishment of a new method to improve the drug delivery by utilization of cadherin peptides by modulating the intercellular junction.

  5. [Effectiveness of interventions for improving drug prescribing in Primary Health Care].

    Science.gov (United States)

    Zavala-González, Marco Antonio; Cabrera-Pivaral, Carlos Enrique; Orozco-Valerio, María de Jesús; Ramos-Herrera, Igor Martín

    2017-01-01

    To determine the effectiveness of interventions for improving drug prescribing in Primary Health Care units. Systematic review and meta-analysis. Searches were made in MedLine(©), ScienceDirect(©), Springer(©), SciELO(©), Dialnet(©), RedALyC(©) and Imbiomed(©), in Spanish, English and Portuguese, using keywords "drug prescribing", "intervention studies" and "primary health care", indexed in each data base up to August 2014. Experimental and quasi-experimental studies were included that had a CASP-score>5 and that evaluated effect of any type intervention on the quality of drug prescription in Primary Health Care. A total of 522 articles were found, and an analysis was performed on 12 that reported 17 interventions: 64.7% educational, 23.5% incorporating pharmacists into the health team, and 11.8% on the use of computer applications. The strong "intervention/improvement" associations were educational interventions OR=2.47 (95% CI; 2.28 - 2.69), incorporation of pharmacists OR=3.28 (95% CI; 2.58 4.18), and use of computer applications OR=10.16 (95% CI; 8.81 -11.71). The use of interventions with computer applications showed to be more effective than educational interventions and incorporation pharmacists into the health team. Future studies are required that include economic variables such as, implementation costs, drug costs and other expenses associated with health care and treatment of diseases. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  6. Parametric time-to-onset models were developed to improve causality assessment of adverse drug reactions from antidiabetic drugs

    NARCIS (Netherlands)

    Scholl, Joep H G; van de Ven, Peter M; van Puijenbroek, Eugène P

    2015-01-01

    OBJECTIVES: The aim of this study was to investigate whether the time to onset (TTO) of common adverse drug reactions (ADRs) of antidiabetic drugs could be modeled using parametric distributions and whether these TTO distributions were dependent on patient characteristics. Furthermore, information r

  7. Improving Drug Loading of Mucosal Solvent Cast Films Using a Combination of Hydrophilic Polymers with Amoxicillin and Paracetamol as Model Drugs

    Directory of Open Access Journals (Sweden)

    Joshua Boateng

    2013-01-01

    Full Text Available Solvent cast mucosal films with improved drug loading have been developed by combining carboxymethyl cellulose (CMC, sodium alginate (SA, and carrageenan (CAR using paracetamol and amoxicillin as model drugs and glycerol (GLY as plasticizer. Films were characterized using X-ray powder diffraction (XRPD, scanning electron microscopy (SEM, folding resilience, swelling capacity, mucoadhesivity, and drug dissolution studies. SA, CMC, and GLY (5 : 3 : 6 films showed maximum amoxicillin loading of 26.3% whilst CAR, CMC, and GLY (1 : 2 : 3 films had a maximum paracetamol loading of 40%. XRPD analysis showed different physical forms of the drugs depending on the amount loaded. Films containing 29.4% paracetamol and 26.3% amoxicillin showed molecular dispersion of the drugs while excess paracetamol was observed on the film surface when the maximum 40% was loaded. Work of adhesion was similar for blank films with slightly higher cohesiveness for CAR and CMC based films, but the differences were significant between paracetamol and amoxicillin containing films. The stickiness and cohesiveness for drug loaded films were generally similar with no significant differences. The maximum percentage cumulative drug release was 84.65% and 70.59% for paracetamol and amoxicillin, respectively, with anomalous case two transport mechanism involving both drug diffusion and polymer erosion.

  8. Benzylpiperidine variations on histamine H3 receptor ligands for improved drug-likeness.

    Science.gov (United States)

    Wingen, Kerstin; Schwed, J Stephan; Isensee, Kathleen; Weizel, Lilia; Zivković, Aleksandra; Odadzic, Dalibor; Odazic, Dalibor; Stark, Holger

    2014-05-15

    Several hH3R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. Nevertheless, many promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity and their dibasic character. Analysis of previously, as potential PET ligands synthesized compounds (ST-889, ST-928) revealed promising results concerning physicochemical properties and drug-likeness. Herein, the synthesis, the evaluation of the binding properties at the hH3R and the estimation of different physicochemical and drug-likeness properties of further novel benzylpiperidine variations on H3R antagonists is described. Due to the introduction of various small hydrophilic moieties in the structure, drug-likeness parameters have been improved. For instance, compound 12 (ST-1032) showed in addition to high affinity at the H3R (pKi (hH3R)=9.3) clogS, clogP, LE, LipE, and LELP values of -2.48, 2.18, 0.44, 7.14, and 4.95, respectively. Also, the keto derivative 5 (ST-1703, pKi (hH3R)=8.6) revealed LipE and LELP values of 5.25 and 6.84, respectively.

  9. Systematic Development of Self-Emulsifying Drug Delivery Systems of Atorvastatin with Improved Bioavailability Potential

    Science.gov (United States)

    Khan, Fariba; Islam, Md. Saiful; Roni, Monzurul Amin; Jalil, Reza-Ul

    2012-01-01

    The aim of this study was to prepare and characterize a self-emulsifying drug delivery system (SEDDS) with a high drug load of poorly water-soluble atorvastatin for the enhancement of dissolution and oral bioavailability. Solubility of atorvastatin in oil, surfactant, and cosurfactant was determined. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations. A high drug load (10% w/w) was achieved with a combination of oleic acid, Tween 80, and polyethylene glycol 400, ensuring the maximum dissolution property (in the case of SES6). Effects of lipids and surfactants on physical properties of SEDDS such as in vitro emulsification efficiency in terms of self-emulsification time, emulsion droplet size, and percent transmittance were measured. Multiple regression analysis revealed that a higher amount of surfactants significantly increased dissolution of ATV while decreasing emulsion droplet size and emulsification time. About a four-fold increase in dissolution was achieved by SEDDS compared to pure ATV powder. Overall, this study suggests that dissolution and oral bioavailability of ATV could be improved by SEDDS technology. PMID:23264948

  10. Engineered particles demonstrate improved flow properties at elevated drug loadings for direct compression manufacturing.

    Science.gov (United States)

    Trementozzi, Andrea N; Leung, Cheuk-Yui; Osei-Yeboah, Frederick; Irdam, Erwin; Lin, Yiqing; MacPhee, J Michael; Boulas, Pierre; Karki, Shyam B; Zawaneh, Peter N

    2017-05-15

    Optimizing powder flow and compaction properties are critical for ensuring a robust tablet manufacturing process. The impact of flow and compaction properties of the active pharmaceutical ingredient (API) becomes progressively significant for higher drug load formulations, and for scaling up manufacturing processes. This study demonstrated that flow properties of a powder blend can be improved through API particle engineering, without critically impacting blend tabletability at elevated drug loadings. In studying a jet milled API (D50=24μm) and particle engineered wet milled API (D50=70μm and 90μm), flow functions of all API lots were similarly poor despite the vast difference in average particle size (ffc10) compared with the jet milled API blends. Investigation of the compaction properties of both wet and jet milled powder blends also revealed that both jet and wet milled material produced robust tablets at the drug loadings used. The ability to practically demonstrate this uncommon observation that similarly poor flowing APIs can lead to a marked difference upon blending is important for pharmaceutical development. It is especially important in early phase development during API selection, and is advantageous particularly when material-sparing techniques are utilized. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Improved dissolution behavior of lipophilic drugs by solid dispersions : the production process as starting point for formulation considerations

    NARCIS (Netherlands)

    Srinarong, Parinda; de Waard, Hans; Frijlink, Henderik W.; Hinrichs, Wouter L. J.

    2011-01-01

    Introduction: Many new drug substances have low aqueous solubility which can cause poor bioavailability after oral administration. The application of solid dispersions is a useful method to increase the dissolution rate of these drugs and thereby improve their bioavailability. So far, several method

  12. User-centered design improves the usability of drug-drug interaction alerts: Experimental comparison of interfaces.

    Science.gov (United States)

    Luna, Daniel R; Rizzato Lede, Daniel A; Otero, Carlos M; Risk, Marcelo R; González Bernaldo de Quirós, Fernán

    2017-02-01

    Clinical Decision Support Systems can alert health professionals about drug interactions when they prescribe medications. The Hospital Italiano de Buenos Aires in Argentina developed an electronic health record with drug-drug interaction alerts, using traditional software engineering techniques and requirements. Despite enhancing the drug-drug interaction knowledge database, the alert override rate of this system was very high. We redesigned the alert system using user-centered design (UCD) and participatory design techniques to enhance the drug-drug interaction alert interface. This paper describes the methodology of our UCD. We used crossover method with realistic, clinical vignettes to compare usability of the standard and new software versions in terms of efficiency, effectiveness, and user satisfaction. Our study showed that, compared to the traditional alert system, the UCD alert system was more efficient (alerts faster resolution), more effective (tasks completed with fewer errors), and more satisfying. These results indicate that UCD techniques that follow ISO 9241-210 can generate more usable alerts than traditional design.

  13. Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres.

    Science.gov (United States)

    Shen, Zheyu; Li, Yan; Kohama, Kazuhiro; Oneill, Brian; Bi, Jingxiu

    2011-01-01

    Folic acid-conjugated albumin nanospheres (FA-AN) have been developed to provide an actively targetable drug delivery system for improved drug targeting of cancer cells with reduced side effects. The nanospheres were prepared by conjugating folic acid onto the surface of albumin nanospheres using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as a catalyst. To test the efficacy of these nanospheres as a potential delivery platform, doxorubicin-loaded albumin nanospheres (DOX-AN) and doxorubicin-loaded FA-AN (FA-DOX-AN) were prepared by entrapping DOX (an anthracycline, antibiotic drug widely used in cancer chemotherapy that works by intercalating DNA) into AN and FA-AN nanoparticles. Cell uptake of the DOX was then measured. The results show that FA-AN was incorporated into HeLa cells (tumor cells) only after 2.0h incubation, whereas HeLa cells failed to incorporate albumin nanospheres without conjugated folic acid after 4.0h incubation. When HeLa cells were treated with the DOX-AN, FA-DOX-AN nanoparticles or free DOX, cell viability decreased with increasing culture time (i.e. cell death increases with time) over a 70h period. Cell viability was always the lowest for free DOX followed by FA-DOX-AN4 and then DOX-AN. In a second set of experiments, HeLa cells washed to remove excess DOX after an initial incubation for 2h were incubated for 70h. The corresponding cell viability was slightly higher when the cells were treated with FA-DOX-AN or free DOX whilst cells treated with DOX-AN nanoparticles remained viable. The above experiments were repeated for non-cancerous, aortic smooth muscle cells (AoSMC). As expected, cell viability of the HeLa cells (with FA receptor alpha, FRα) and AoSMC cells (without FRα) decreased rapidly with time in the presence of free DOX, but treatment with FA-DOX-AN resulted in selective killing of the tumor cells. These results indicated that FA-AN may be used as a promising actively targetable drug delivery system to improve drug

  14. Colloidal silver nanoparticles improve anti-leukemic drug efficacy via amplification of oxidative stress.

    Science.gov (United States)

    Guo, Dawei; Zhang, Junren; Huang, Zhihai; Jiang, Shanxiang; Gu, Ning

    2015-02-01

    Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy.

  15. Improving co-amorphous drug formulations by the addition of the highly water soluble amino acid proline

    DEFF Research Database (Denmark)

    Jensen, Katrine Birgitte Tarp; Löbmann, Korbinian; Rades, Thomas;

    2014-01-01

    by combining the model drug, naproxen (NAP), with an amino acid to physically stabilize the co-amorphous system (tryptophan, TRP, or arginine, ARG) and a second highly soluble amino acid (proline, PRO) for an additional improvement of the dissolution rate. Co-amorphous drug-amino acid blends were prepared......Co-amorphous drug amino acid mixtures were previously shown to be a promising approach to create physically stable amorphous systems with the improved dissolution properties of poorly water-soluble drugs. The aim of this work was to expand the co-amorphous drug amino acid mixture approach...... by ball milling and investigated for solid state characteristics, stability and the dissolution rate enhancement of NAP. All co-amorphous mixtures were stable at room temperature and 40 °C for a minimum of 84 days. PRO acted as a stabilizer for the co-amorphous system, including NAP–TRP, through enhancing...

  16. Flavonoids and polymer derivatives as CYP3A4 inhibitors for improved oral drug bioavailability.

    Science.gov (United States)

    Fasinu, Pius; Choonara, Yahya E; Khan, Riaz A; Du Toit, Lisa C; Kumar, Pradeep; Ndesendo, Valence M K; Pillay, Viness

    2013-02-01

    Molecular modeling computations were utilized to generate pharmaceutical grade CYP3A4-enzyme inhibitors. In vitro metabolism of felodipine in human intestinal and liver microsomes (HLM and HIM) was optimized yielding a Michaelis-Menten plot from where the K(m) and V(max) values were estimated by nonlinear regression. The flavonoids, naringin, naringenin, and quercetin, were subsequently incubated with felodipine at the determined K(m) value in HLM. Comparing results obtained from a known CYP3A4 inhibitor, verapamil, the flavonoids inhibited felodipine metabolism. In-depth computational analysis of these flavonoids in terms of CYP3A4 binding, sequencing, and affinity, computational biomimetism was employed to validate the potential CYP3A4 inhibitors. The modeled compounds were comparatively evaluated by incubation with felodipine in both HLM and HIM. Results showed that the polymers 8-arm-PEG, o-(2-aminoethyl)-o-methyl-PEG, 4-arm-PEG (molecular weight = 10,000 g/mol and 20,000 g/mol, respectively), and poly(l-lysine) were able to inhibit the felodipine metabolism with the half maximal inhibitory concentration (IC(50)) values ranging from 7.22 to 30.0 μM (HLM) and 5.78 to 41.03 μM (HIM). Molecular docking confirmed drug-enzyme interactions by computing the free energies of binding (ΔE) and inhibition constants (K(i)) of the docked compounds utilizing a Lamarckian Genetic Algorithm. Comparative correlations between the computed and experimental K(i) values were obtained. Computational modeling of CYP3A4 inhibitors provided a suitable strategy to screen pharmaceutical grade compounds that may potentially inhibit presystemic CYP3A4-dependent drug metabolism with the prospect of improving oral drug bioavailability. Copyright © 2012 Wiley Periodicals, Inc.

  17. Safety Learning From Drugs of the Same Class : Room for Improvement

    NARCIS (Netherlands)

    Stefansdottir, G.; Knol, M. J.; Arnardottir, A. H.; van der Elst, M. E.; Grobbee, D. E.; Leufkens, H. G. M.; De Bruin, M. L.

    This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs)

  18. Amorphous ternary cyclodextrin nanocomposites of telmisartan for oral drug delivery: improved solubility and reduced pharmacokinetic variability.

    Science.gov (United States)

    Sangwai, Mayur; Vavia, Pradeep

    2013-09-10

    Despite of advancements in dosage form design and use of multifunctional excipients, improvement in dissolution characteristics of molecules like Telmisartan (TEL) having exceedingly pH dependent and poor solubility profile is still challenging. The present research work explores an innovative particle engineering approach which synergistically coalesce two principally different solubility enhancement strategies namely ternary β-cyclodextrin complexation and top-down nanonization in a unit process. The research was aimed to improve solubility and reduce in vivo variability in pharmacokinetic parameters of TEL irrespective to physiological pH conditions. Ternary β-cyclodextrin nanocomposites of TEL were prepared with high pressure homogenization using meglumine as ternary component. TEL nanocomposites were thoroughly characterized for particle size, surface topology, surface charge, inclusion complexation, crystalinity, dissolution and in vivo pharmacokinetic performance in male wistar rats at fed and fasted state. TEL nanocomposites exhibited average particle size of 698 ± 23 nm. Remarkable improvement in in vitro dissolution characteristics in multimedia and biorelevant media was observed in comparison with plain drug and marketed formulation. Results of in vivo pharmacokinetic studies revealed that, nanocomposites effectively bypass variation in pharmacokinetic parameters at fed and fasted states with 346%, 315%, 301% and 321% increase in relative bioavailability compared to marketed formulation and pure TEL in fed and fasted conditions respectively.

  19. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion.

    Science.gov (United States)

    Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio

    2015-11-01

    Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.

  20. Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

    Directory of Open Access Journals (Sweden)

    Fang Li

    2017-05-01

    Full Text Available Huperzine A (Hup-A is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve (AUC of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0.01. The absorption rate constant (Ka and the apparent permeability coefficient (Papp for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of Ka and Papp of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration (Cmax of the blocking model were significantly lower than those of the control model (P<0.05. The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

  1. Exploiting the Immunomodulatory Properties of Chemotherapeutic Drugs to Improve the Success of Cancer Immunotherapy.

    Science.gov (United States)

    Kersten, Kelly; Salvagno, Camilla; de Visser, Karin E

    2015-01-01

    Cancer immunotherapy is gaining momentum in the clinic. The current challenge is to understand why a proportion of cancer patients do not respond to cancer immunotherapy, and how this can be translated into the rational design of combinatorial cancer immunotherapy strategies aimed at maximizing success of immunotherapy. Here, we discuss how tumors orchestrate an immunosuppressive microenvironment, which contributes to their escape from immune attack. Relieving the immunosuppressive networks in cancer patients is an attractive strategy to extend the clinical success of cancer immunotherapy. Since the clinical availability of drugs specifically targeting immunosuppressive cells or mediators is still limited, an alternative strategy is to use conventional chemotherapy drugs with immunomodulatory properties to improve cancer immunotherapy. We summarize the preclinical and clinical studies that illustrate how the anti-tumor T cell response can be enhanced by chemotherapy-induced relief of immunosuppressive networks. Treatment strategies aimed at combining chemotherapy-induced relief of immunosuppression and T cell-boosting checkpoint inhibitors provide an attractive and clinically feasible approach to overcome intrinsic and acquired resistance to cancer immunotherapy, and to extend the clinical success of cancer immunotherapy.

  2. THE USE OF SELECTED ANAESTHETIC DRUGS IN SEARCH OF A METHOD FOR IMPROVING EARTHWORMS’ WELFARE

    Directory of Open Access Journals (Sweden)

    Agnieszka Podolak-Machowska

    2013-07-01

    Full Text Available This paper describes selected effects of body contact of earthworms Dendrobaena veneta Rosa with local anaesthetic (LA drugs used for human anesthesia (lidocaine and prilocaine and anaesthetics for aquatic animals (MS-222. The findings showed safe and effective immobilization of earthworms with prilocaine at a concentration of 0.25-1%. At the applied concentrations lidocaine was safe, but less effective. On the other hand, MS-222, at the applied concentrations had a strongly irritating effect for earthworms and induced convulsive body movements connected with a discharge of coelomic fluid. The results may be relevant both for improving the welfare of earthworms during experiments and for the organization of research involving testing drugs on invertebrates. In this case, by using earthworms as an experimental model and by applying the method for measuring their mobility after contact with anaesthetics, which has been described in this article, it might be possible to replace experiments on guinea pigs, rabbits, rats and mice, which are expensive and require an approval of an ethics committee, with laboratory tests on earthworms.

  3. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

    Science.gov (United States)

    Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli; Liu, Jianping

    2016-09-01

    Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10-100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer-polymer and polymer-cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.

  4. Adding a Prescription Drug Benefit to Medicare: An Analysis of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003

    Science.gov (United States)

    2004-09-01

    unpredictable and potentially high costs ( Marmor , 2000). The missing benefit was outpatient prescription drug coverage. On July 30th, President Johnson...Proposed Medicare Benefit At-a-Glance Chart. Retrieved September 12, 2004, from: http://www.kff.org/medicare/ medicarebenefitataglance.cfm Marmor , T.R

  5. Effectiveness of the behavior change intervention to improve harm reduction self-efficacy among people who inject drugs in Thailand

    Directory of Open Access Journals (Sweden)

    Pawa D

    2016-09-01

    Full Text Available Duangta Pawa,1 Chitlada Areesantichai1,2 1College of Public Health Sciences, Chulalongkorn University, 2Drug Dependence Research Center WHO Collaborating Centre for Research and Training in Drug Dependence, Bangkok, Thailand Background: People who inject drugs (PWID in Thailand reported unsafe injection practices resulting in injection-related health consequences. Harm reduction self-efficacy plays an important role and could be improved to reduce harm associated with injecting drugs. Evidence-based interventions targeting PWID are needed. This study sought to evaluate the effectiveness of the behavior change intervention within the PWID population. Methods: The behavior change intervention, Triple-S, was designed to improve harm reduction self-efficacy among PWID. This quasi-experimental study was a pre- and post-comparison with a control group design. Participants were PWID, aged 18–45 years, and located in Bangkok. Changes in harm reduction self-efficacy of the intervention group were compared with the control group using paired and independent t-test. Results: Most of PWID were male (84%, had a secondary school and lower education (71%, were single, and had a mean age of 41 years. They had been injecting drugs for an average of 20 years, and the median of drug injections per week was ten times in the past month. Pre- and post-intervention effects were measured and results showed that the intervention group reported improvement in harm reduction self-efficacy in negative emotional conditions (P=0.048. Conclusion: Our findings suggest that Triple-S intervention can significantly improve harm reduction self-efficacy in negative emotional conditions. The results may suggest the importance of behavior change intervention, especially when integrated with services provided by drop-in centers. The intervention can be further developed to cover other harm reduction behaviors and improve harm reduction self-efficacy. Keywords: drug injection, harm

  6. Improving toxicity screening and drug development by using genetically defined strains.

    Science.gov (United States)

    Festing, Michael F W

    2010-01-01

    According to the US Food and Drugs Administration (Food and Drug Administration (2004) Challenge and opportunity on the critical path to new medical products.) "The inability to better assess and predict product safety leads to failures during clinical development and, occasionally, after marketing". This increases the cost of new drugs as clinical trials are even more expensive than pre-clinical testing.One relatively easy way of improving toxicity testing is to improve the design of animal experiments. A fundamental principle when designing an experiment is to control all variables except the one of interest: the treatment. Toxicologist and pharmacologists have widely ignored this principle by using genetically heterogeneous "outbred" rats and mice, increasing the chance of false-negative results. By using isogenic (inbred or F1 hybrid, see Note 1) rats and mice instead of outbred stocks the signal/noise ratio and the power of the experiments can be increased at little extra cost whilst using no more animals. Moreover, the power of the experiment can be further increased by using more than one strain, as this reduces the chance of selecting one which is resistant to the test chemical. This can also be done without increasing the total number of animals by using a factorial experimental design, e.g. if the ten outbred animals per treatment group in a 28-day toxicity test were replaced by two animals of each of five strains (still ten animals per treatment group) selected to be as genetically diverse as possible, this would increase the signal/noise ratio and power of the experiment. This would allow safety to be assessed using the most sensitive strain.Toxicologists should also consider making more use of the mouse instead of the rat. They are less costly to maintain, use less test substance, there are many inbred and genetically modified strains, and it is easier to identify gene loci controlling variation in response to xenobiotics in this species.We demonstrate

  7. A pilot randomized controlled clinical trial to improve antiepileptic drug adherence in young children with epilepsy.

    Science.gov (United States)

    Modi, Avani C; Guilfoyle, Shanna M; Mann, Krista A; Rausch, Joseph R

    2016-03-01

    The primary aim was to examine the preliminary efficacy of a family tailored problem-solving intervention to improve antiepileptic drug (AED) adherence in families of children with new-onset epilepsy. Secondary aims were to assess changes in targeted mechanisms and treatment feasibility and acceptability. Fifty families (M(age) = 7.6 ± 3.0; 80% Caucasian; 42% idiopathic localization related) completed baseline questionnaires and were given an electronic monitor to observe daily AED adherence. If adherence was ≤ 95% in the first 7 months of the study, families were randomized (Supporting Treatment Adherence Regimens (STAR): n = 11; Treatment as Usual (TAU): n = 12). Twenty-one families were not randomized due to adherence being ≥95%. The STAR intervention included four face-to-face and two telephone problem-solving sessions over 8 weeks. Significant group differences in adherence were found during active intervention (weeks 4-6; TAU = -12.0 vs. STAR = 18.1, p < 0.01; and weeks session 6-8: TAU = -9.7 vs. STAR = 15.3, p < 0.05). Children who received the STAR intervention exhibited improved adherence compared to children in the TAU group during active treatment. Significant changes in epilepsy knowledge and management were noted for the STAR group. Families expressed benefitting from the STAR intervention. Future studies should include a larger sample size and booster intervention sessions to maintain treatment effects over time.

  8. An educational intervention to improve nurses' knowledge, attitude, and practice toward reporting of adverse drug reactions.

    Science.gov (United States)

    Hanafi, Somayeh; Torkamandi, Hassan; Hayatshahi, Alireza; Gholami, Kheirollah; Shahmirzadi, Nikinaz Ashrafi; Javadi, Mohammad Reza

    2014-01-01

    The reporting of adverse drug reactions (ADRs) by nurses in hospitals is very important. This study was aimed at investigating the impact of an educational intervention to improve ADR reporting and whether trained nurses had better knowledge, attitude, and practice toward ADR reporting. A total of 300 nurses in a tertiary care teaching hospital in Tehran, Iran were evaluated with a knowledge, attitude, and practice (KAP) questionnaire regarding ADR reporting in March 2010. After this, an educational program about ADR was provided to nurses. Then the nurses were re-evaluated by the same questionnaire. Comparisons were made of the attitude and knowledge within nurses, before and after education. Data were analyzed using SPSS software. P < 0.05 was considered as significant level. Independent-sample t-test was used to measure the intervention effect. The response rate was 61.3% (N = 184). Knowledge of nurses before the intervention was significantly less than the knowledge after the intervention (P = 0.001). Also, there was a significant effect on attitude (P = 0.002). During the follow-up period of 4 months after the intervention, 26 spontaneous reports were received. Continuous ADR educational program, training, and integration of ADRs' reporting into the activities of the nurses would likely improve ADR reporting.

  9. Drug resistance marker-aided genome shuffling to improve acetic acid tolerance in Saccharomyces cerevisiae.

    Science.gov (United States)

    Zheng, Dao-Qiong; Wu, Xue-Chang; Wang, Pin-Mei; Chi, Xiao-Qin; Tao, Xiang-Lin; Li, Ping; Jiang, Xin-Hang; Zhao, Yu-Hua

    2011-03-01

    Acetic acid existing in a culture medium is one of the most limiting constraints in yeast growth and viability during ethanol fermentation. To improve acetic acid tolerance in Saccharomyces cerevisiae strains, a drug resistance marker-aided genome shuffling approach with higher screen efficiency of shuffled mutants was developed in this work. Through two rounds of genome shuffling of ultraviolet mutants derived from the original strain 308, we obtained a shuffled strain YZ2, which shows significantly faster growth and higher cell viability under acetic acid stress. Ethanol production of YZ2 (within 60 h) was 21.6% higher than that of 308 when 0.5% (v/v) acetic acid was added to fermentation medium. Membrane integrity, higher in vivo activity of the H+-ATPase, and lower oxidative damage after acetic acid treatment are the possible reasons for the acetic acid-tolerance phenotype of YZ2. These results indicated that this novel genome shuffling approach is powerful to rapidly improve the complex traits of industrial yeast strains.

  10. Could a revision of the current guidelines for cancer drug use improve the quality of cancer treatment?

    Directory of Open Access Journals (Sweden)

    Lippert TH

    2014-01-01

    Full Text Available Theodor H Lippert,1 Hans-Jörg Ruoff,1 Manfred Volm2 1Medical Faculty, University of Tübingen, Tübingen, Germany; 2Medical Faculty, University of Heidelberg, Heidelberg, Germany Abstract: Clinical practice guidelines are indispensable for such a variable disease as malignant solid tumors, with the complex possibilities of drug treatment. The current guidelines may be criticized on several points, however. First, there is a lack of information on the outcome of treatment, such as the expected success and failure rates. Treating not only drug responders but also nonresponders, that is, patients with drug resistance, must result in failures. There is no mention of the possibility of excluding the drug nonresponders, identifiable by special laboratory tests and no consideration is given to the different side effects of the recommended drug regimens. Nor are there any instructions concerning tumor cases for which anticancer drug treatment is futile. In such cases, early palliative care may lead to significant improvements in both life quality and life expectancy. Not least, there is no transparency concerning the preparation of the guidelines: persons cannot be identified who could give a statement of conflicts of interest, and responsibility is assumed only by anonymous medical associations. A revision of the current guidelines could considerably improve cancer treatment. Keywords: anticancer drugs, quality of guidelines, critical remarks

  11. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young [College of Medicine, Korea University, Guro Hospital, Seoul (Korea, Republic of)

    2008-04-15

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  12. Production of Inhalable Submicrometer Aerosols from Conventional Mesh Nebulizers for Improved Respiratory Drug Delivery.

    Science.gov (United States)

    Longest, P Worth; Spence, Benjamin M; Holbrook, Landon T; Mossi, Karla M; Son, Yoen-Ju; Hindle, Michael

    2012-09-01

    Submicrometer and nanoparticle aerosols may significantly improve the delivery efficiency, dissolution characteristics, and bioavailability of inhaled pharmaceuticals. The objective of this study was to explore the formation of submicrometer and nanometer aerosols from mesh nebulizers suitable for respiratory drug delivery using experiments and computational fluid dynamics (CFD) modeling. Mesh nebulizers were coupled with add-on devices to promote aerosol drying and the formation of submicrometer particles, as well as to control the inhaled aerosol temperature and relative humidity. Cascade impaction experiments were used to determine the initial mass median aerodynamic diameters of 0.1% albuterol aerosols produced by the AeroNeb commercial (4.69 μm) and lab (3.90 μm) nebulizers and to validate the CFD model in terms of droplet evaporation. Through an appropriate selection of flow rates, nebulizers, and model drug concentrations, submicrometer and nanometer aerosols could be formed with the three devices considered. Based on CFD simulations, a wire heated design was shown to overheat the airstream producing unsafe conditions for inhalation if the aerosol was not uniformly distributed in the tube cross-section or if the nebulizer stopped producing droplets. In comparison, a counter-flow heated design provided sufficient thermal energy to produce submicrometer particles, but also automatically limited the maximum aerosol outlet temperature based on the physics of heat transfer. With the counter-flow design, submicrometer aerosols were produced at flow rates of 5, 15, and 30 LPM, which may be suitable for various forms of oral and nasal aerosol delivery. Thermodynamic conditions of the aerosol stream exiting the counter-flow design were found be in a range of 21-45 °C with relative humidity greater than 40% in some cases, which was considered safe for direct inhalation and advantageous for condensational growth delivery.

  13. Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia

    Directory of Open Access Journals (Sweden)

    Tomiki eSumiyoshi

    2013-10-01

    Full Text Available Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT receptors in ameliorating cognitive deficits of schizophrenia.It is noteworthy that atypical antipsychotic drugs, e.g. clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and GABA neurons. A novel strategy for cognitive enhancement in psychosis may be benefitted by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g. event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs acting directly or indirectly on 5-HT1A receptors.These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

  14. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very

  15. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs.

    Science.gov (United States)

    Dahan, Arik; Hoffman, Amnon

    2008-07-02

    As a consequence of modern drug discovery techniques, there has been a consistent increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered medications with sufficient bioavailability. One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based drug delivery system. Unfortunately, current development strategies in the area of lipid based delivery systems are mostly empirical. Hence, there is a need for a simplified in vitro method to guide the selection of a suitable lipidic vehicle composition and to rationalize the delivery system design. To address this need, a dynamic in vitro lipolysis model, which provides a very good simulation of the in vivo lipid digestion process, has been developed over the past few years. This model has been extensively used for in vitro assessment of different lipid based delivery systems, leading to enhanced understanding of the suitability of different lipids and surfactants as a delivery system for a given poorly water soluble drug candidate. A key goal in the development of the dynamic in vitro lipolysis model has been correlating the in vitro data of various drug-lipidic delivery system combinations to the resultant in vivo drug profile. In this paper, we discuss and review the need for this model, its underlying theory, practice and limitations, and the available data accumulated in the literature. Overall, the dynamic in vitro lipolysis model seems to provide highly useful initial guidelines in the development process of oral lipid based drug delivery systems for poorly water soluble drugs, and it predicts phenomena that occur in the pre-enterocyte stages of the intestinal absorption cascade.

  16. 麻醉科毒麻精神药品管理的改进与体会%Improved Drug Hemp and Experience Anesthesiology Management of Psychotropic Drugs

    Institute of Scientific and Technical Information of China (English)

    张云; 郑艳萍; 周艳

    2014-01-01

    Ensure the safe use of toxic hemp drugs is an important part of the work of drug administration in anesthesiology department. During our work, we found that there are some loopholes in administration of toxic hemp psychotropic drugs in anesthesiology department of our hospital. We propose a combination of the psychotropic drugs management experience from anesthesiology department of PLA general hospital and drug hemp content in spiritual Narcotic Drugs and Drug Regulations, to improve and perfect the regulation of anesthesiology department. The operating room nurses are united with anesthesiology nurses, to jointly manage toxic hemp medicines and ensure that every aspect of the use of psychotropic drugs is under the control of regulation, to prevent the outlfow of narcotic drugs, and to ensure that the process of psychotropic drugs use in security, legalization, standardized and orderly.%保证毒麻药品的安全使用是麻醉科药品管理工作的重要内容之一,在工作中发现我院麻醉科毒麻精神药品管理存在一些漏洞。现将解放军总医院麻醉科毒麻精神药品的管理经验与《麻醉药品精神药品管理条例》内容相结合,对我院麻醉科的管理制度进行改进与完善,联合麻醉科护士与手术室护士共同对毒麻药品进行管理,确保毒麻药品精神药品每个使用环节都有监管,杜绝麻醉药品外流。保证毒麻精神药品使用过程中的安全性、合法化、规范化、有序化。

  17. Polyelectrolyte Complex Based Interfacial Drug Delivery System with Controlled Loading and Improved Release Performance for Bone Therapeutics

    Directory of Open Access Journals (Sweden)

    David Vehlow

    2016-03-01

    Full Text Available An improved interfacial drug delivery system (DDS based on polyelectrolyte complex (PEC coatings with controlled drug loading and improved release performance was elaborated. The cationic homopolypeptide poly(l-lysine (PLL was complexed with a mixture of two cellulose sulfates (CS of low and high degree of substitution, so that the CS and PLL solution have around equal molar charged units. As drugs the antibiotic rifampicin (RIF and the bisphosphonate risedronate (RIS were integrated. As an important advantage over previous PEC systems this one can be centrifuged, the supernatant discarded, the dense pellet phase (coacervate separated, and again redispersed in fresh water phase. This behavior has three benefits: (i Access to the loading capacity of the drug, since the concentration of the free drug can be measured by spectroscopy; (ii lower initial burst and higher residual amount of drug due to removal of unbound drug and (iii complete adhesive stability due to the removal of polyelectrolytes (PEL excess component. It was found that the pH value and ionic strength strongly affected drug content and release of RIS and RIF. At the clinically relevant implant material (Ti40Nb similar PEC adhesive and drug release properties compared to the model substrate were found. Unloaded PEC coatings at Ti40Nb showed a similar number and morphology of above cultivated human mesenchymal stem cells (hMSC compared to uncoated Ti40Nb and resulted in considerable production of bone mineral. RIS loaded PEC coatings showed similar effects after 24 h but resulted in reduced number and unhealthy appearance of hMSC after 48 h due to cell toxicity of RIS.

  18. Creating a unique, multi-stakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer.

    Science.gov (United States)

    Vassal, Gilles; Rousseau, Raphaël; Blanc, Patricia; Moreno, Lucas; Bode, Gerlind; Schwoch, Stefan; Schrappe, Martin; Skolnik, Jeffrey; Bergman, Lothar; Bradley-Garelik, Mary Brigid; Saha, Vaskar; Pearson, Andy; Zwierzina, Heinz

    2015-01-01

    Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders - academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory pressure to propose early Paediatric Investigation Plans (PIPs), missed opportunities to explore new drugs potentially relevant for paediatric malignancies, lack of innovative trial designs and no new incentives to develop drugs against specific paediatric targets are some unmet needs. Better access to new anti-cancer drugs for paediatric clinical studies and improved collaboration between stakeholders are essential. The Cancer Drug Development Forum (CDDF), previously Biotherapy Development Association (BDA), with Innovative Therapy for Children with Cancer Consortium (ITCC), European Society for Paediatric Oncology (SIOPE) and European Network for Cancer Research in Children and Adolescents (ENCCA) has created a unique Paediatric Oncology Platform, involving multiple stakeholders and the European Union (EU) Commission, with an urgent remit to improve paediatric oncology drug development. The Paediatric Oncology Platform proposes to recommend immediate changes in the implementation of the Regulation and set the framework for its 2017 revision; initiatives to incentivise drug development against specific paediatric oncology targets, and repositioning of drugs not developed in adults. Underpinning these changes is a strategy for mechanism of action and biology driven selection and prioritisation of potential paediatric indications rather than the current process based on adult cancer indications. Pre-competitive research and drug prioritisation, early portfolio evaluation, cross-industry cooperation and multi-compound/sponsor trials are being explored, from which guidance for innovative trial designs will be

  19. Self-Micro Emulsifying Drug Delivery Systems: a Strategy to Improve Oral Bioavailability

    Directory of Open Access Journals (Sweden)

    Vijay K. Sharma

    Full Text Available Aim: Oral route has always been the favorite route of drug administration in many diseases and till today it is the first way investigated in the development of new dosage forms. The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility, thereby pose problems in their formulation. For the therapeutic delivery of lipophilic active moieties (BCS class II drugs, lipid based formulations are inviting increasing attention. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the formulation and development of self-micro emulsifying drug delivery systems as well as its therapeutic activity. Results: Self-emulsifying drug delivery system (SMEDDS has gained more attention due to enhanced oral bio-availability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s toward specific absorption window in GIT, and protection of drug(s from the unreceptive environment in gut. Conclusions: This article gives a complete overview of SMEDDS as a promising approach to effectively deal with the problem of poorly soluble molecules.

  20. Lipid nanoparticles with no surfactant improve oral absorption rate of poorly water-soluble drug.

    Science.gov (United States)

    Funakoshi, Yuka; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2013-07-15

    A pharmacokinetic study was performed in rats to evaluate the oral absorption ratios of nanoparticle suspensions containing the poorly water-soluble compound nifedipine (NI) and two different types of lipids, including hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol. NI-lipid nanoparticle (LN) suspensions with a mean particle size of 48.0 nm and a zeta potential of -57.2 mV were prepared by co-grinding combined with a high-pressure homogenization process. The oral administration of NI-LN suspensions to rats led to a significant increase in the NI plasma concentration, and the area under the curve (AUC) value was found to be 108 min μg mL⁻¹, indicating a 4-fold increase relative to the NI suspensions. A comparison of the pharmacokinetic parameters of the NI-LN suspensions with those of the NI solution prepared using only the surfactant polysorbate 80 revealed that although the AUC and bioavailability (59%) values were almost identical, a rapid absorption rate was still observed in the NI-LN suspensions. These results therefore indicated that lipid nanoparticles prepared using only two types of phospholipid with a mean particle size of less than 50 nm could improve the absorption of the poorly water-soluble drug. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy.

    Science.gov (United States)

    Fan, Yuchen; Moon, James J

    2015-01-01

    Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens) and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  2. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Yuchen Fan

    2015-08-01

    Full Text Available Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  3. Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia.

    Science.gov (United States)

    Sumiyoshi, Tomiki; Higuchi, Yuko; Uehara, Takashi

    2013-10-16

    Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT) receptors in ameliorating cognitive deficits of schizophrenia. It is noteworthy that atypical antipsychotic drugs (AAPDs), e.g., clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence. The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and gamma-aminobutyric acid neurons. A novel strategy for cognitive enhancement in psychosis may be benefited by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g., event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some AAPDs acting directly or indirectly on 5-HT1A receptors. These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

  4. Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading.

    Science.gov (United States)

    Han, Xi; Ghoroi, Chinmay; Davé, Rajesh

    2013-02-14

    Motivated by our recent study showing improved flow and dissolution rate of the active pharmaceutical ingredient (API) powders (20 μm) produced via simultaneous micronization and surface modification through continuous fluid energy milling (FEM) process, the performance of blends and direct compacted tablets with high drug loading is examined. Performance of 50 μm API powders dry coated without micronization is also considered for comparison. Blends of micronized, non-micronized, dry coated or uncoated API powders at 30, 60 and 70% drug loading, are examined. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density compared to the blends containing uncoated API, which are required for direct compaction. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, as seen in the proposed bulk density-FFC phase map. Dry coating led to improved tablet compactibility profiles, corresponding with the improvements in blend compressibility. The most significant advantage is in tablet dissolution where for all drug loadings, the t(80) for the tablets with dry coated APIs was well under 5 min, indicating that this approach can produce nearly instant release direct compacted tablets at high drug loadings.

  5. Improvement of drug delivery by hyperthermia treatment using magnetic cubic cobalt ferrite nanoparticles

    Science.gov (United States)

    Dey, Chaitali; Baishya, Kaushik; Ghosh, Arup; Goswami, Madhuri Mandal; Ghosh, Ajay; Mandal, Kalyan

    2017-04-01

    In this study, we report a novel synthesis method, characterization and application of a new class of ferromagnetic cubic cobalt ferrite magnetic nanoparticles (MNPs) for hyperthermia therapy and temperature triggered drug release. The MNPs are characterized by XRD, TEM, FESEM, AC magnetic hysteresis and VSM. These MNPs were coated with folic acid and loaded with an anticancer drug. The drug release studies were done at two different temperatures (37 °C and 44 °C) with progress of time. It was found that higher release of drug took place at elevated temperature (44 °C). We have developed a temperature sensitive drug delivery system which releases the heat sensitive drug selectively as the particles are heated up under AC magnetic field and controlled release is possible by changing the external AC magnetic field.

  6. Nanoparticle Drug Loading as a Design Parameter to Improve Docetaxel Pharmacokinetics and Efficacy

    OpenAIRE

    Chu, Kevin S.; Schorzman, Allison N.; Finniss, Mathew C.; Bowerman, Charles J.; Peng, Lei; Luft, J. Christopher; Madden, Andrew; Wang, Andrew Z.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to ...

  7. Overview of milling techniques for improving the solubility of poorly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Zhi Hui Loh

    2015-07-01

    Full Text Available Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a “top–down” approach in the production of fine particles. Fine drug particulates are especially desired in formulations designed for parenteral, respiratory and transdermal use. Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents, often to enhance processability or solubility especially for drugs with limited aqueous solubility. The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size, specific surface area and shape of the drug particles as well as milling-induced amorphization and/or structural disordering of the drug crystal (mechanochemical activation. Technology advancements in milling now enable the production of drug micro- and nano-particles on a commercial scale with relative ease. This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs. Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.

  8. IMPROVING THE SOLUBILITY OF ANTIHELMINTIC DRUG BY SOLID DISPERSIONS AND INCLUSION COMPLEXES

    Directory of Open Access Journals (Sweden)

    Kumar Vijay

    2011-08-01

    Full Text Available Fenbendazole is an Antihelmintic drug (BCS class 2 and poorly soluble in water. Fenbendazole is used as a model drug. This study was conducted to enhance the bioavailability by increasing the aqueous solubility of Fenbendazole. The solid dispersions were prepared with polyvinylpyrrolidone K-25 (PVP K25 and Urea, Inclusion complexes with beta-cyclodextrin (BCD. Solid dispersions and inclusion complexes are prepared by Kneading and Solvent evaporation methods using different drug-polymer ratio like 1:2, 1:4and 1:6. The prepared formulations were characterized for FTIR, drug content, Phase solubility, percent yield and in vitro release studies followed by various release kinetics. The drug content uniformity was found to be good in all formulations. Kinetic profile showed good linearity with first order i.e. exhibiting concentration dependent release of drug. The result indicated that the solubility and dissolution rates of all formulation were significantly increased by solid dispersions and cyclodextrin complexes when compare to pure drug. Dissolution of the pure drug more with beta cyclodextrin complexes than solid dispersion (PVPK25 and Urea. Among all the formulations, VA3 drug-beta-cyclodextrin ratio was found to be better. The result confirmed that beta-cyclodextrin (BCD showed better solubility and dissolution characteristics when compared to polyvinylpyrrolidone K-25 (PVP K25 and Urea.

  9. Improving drug delivery strategies for lymphatic filariasis elimination in urban areas in Ghana.

    Directory of Open Access Journals (Sweden)

    Nana-Kwadwo Biritwum

    2017-05-01

    Full Text Available The Global Program to Eliminate Lymphatic Filariasis (GPELF advocates for the treatment of entire endemic communities, in order to achieve its elimination targets. LF is predominantly a rural disease, and achieving the required treatment coverage in these areas is much easier compared to urban areas that are more complex. In Ghana, parts of the Greater Accra Region with Accra as the capital city are also endemic for LF. Mass Drug Administration (MDA in Accra started in 2006. However, after four years of treatment, the coverage has always been far below the 65% epidemiologic coverage for interrupting transmission. As such, there was a need to identify the reasons for poor treatment coverage and design specific strategies to improve the delivery of MDA. This study therefore set out to identify the opportunities and barriers for implementing MDA in urban settings, and to develop appropriate strategies for MDA in these settings. An experimental, exploratory study was undertaken in three districts in the Greater Accra region. The study identified various types of non-rural settings, the social structures, stakeholders and resources that could be employed for MDA. Qualitative assessment such as in-depth interviews (IDIs and focus group discussions (FGDs with community leaders, community members, health providers, NGOs and other stakeholders in the community was undertaken. The study was carried out in three phases: pre-intervention, intervention and post-intervention phases, to assess the profile of the urban areas and identify reasons for poor treatment coverage using both qualitative and quantitative research methods. The outcomes from the study revealed that, knowledge, attitudes and practices of community members to MDA improved slightly from the pre-intervention phase to the post-intervention phase, in the districts where the interventions were readily implemented by health workers. Many factors such as adequate leadership, funding, planning and

  10. Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes.

    Science.gov (United States)

    Yu, Debin; Zhao, Mingzhi; Dong, Liwei; Zhao, Lu; Zou, Mingwei; Sun, Hetong; Zhang, Mengying; Liu, Hongyu; Zou, Zhihua

    2016-01-01

    Type III interferons (IFNs) (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the expression of the antiviral genes MxA and OAS and two of them, analog-6 and -7, displayed an unexpected high potency that is higher than that of type I IFN (IFN-α2a) in activating the IFN-stimulated response element (ISRE)-luciferase reporter. Importantly, both analog-6 and -7 effectively inhibited replication of hepatitis C virus in Huh-7.5.1 cells, with an IC50 that is comparable to that of IFN-α2a; and consistent with the roles of IFN-λ in mucosal epithelia, both analogs potently inhibited replication of H3N2 influenza A virus in A549 cells. Together, these studies identified two IFN-λ analogs as candidates to be developed as novel antiviral biologics.

  11. Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

    Science.gov (United States)

    Yu, Debin; Zhao, Mingzhi; Dong, Liwei; Zhao, Lu; Zou, Mingwei; Sun, Hetong; Zhang, Mengying; Liu, Hongyu; Zou, Zhihua

    2016-01-01

    Type III interferons (IFNs) (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the expression of the antiviral genes MxA and OAS and two of them, analog-6 and -7, displayed an unexpected high potency that is higher than that of type I IFN (IFN-α2a) in activating the IFN-stimulated response element (ISRE)-luciferase reporter. Importantly, both analog-6 and -7 effectively inhibited replication of hepatitis C virus in Huh-7.5.1 cells, with an IC50 that is comparable to that of IFN-α2a; and consistent with the roles of IFN-λ in mucosal epithelia, both analogs potently inhibited replication of H3N2 influenza A virus in A549 cells. Together, these studies identified two IFN-λ analogs as candidates to be developed as novel antiviral biologics. PMID:26792983

  12. Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

    Directory of Open Access Journals (Sweden)

    Yu D

    2016-01-01

    Full Text Available Debin Yu,1 Mingzhi Zhao,2 Liwei Dong,1 Lu Zhao,1 Mingwei Zou,3 Hetong Sun,4 Mengying Zhang,4 Hongyu Liu,4 Zhihua Zou1 1National Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 2State Key Laboratory of Proteomics, National Engineering Research Center for Protein Drugs, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3Department of Psychology, College of Liberal Arts and Social Sciences, University of Houston, Houston, TX, USA; 4Prosit Sole Biotechnology, Co., Ltd., Beijing, People’s Republic of China Abstract: Type III interferons (IFNs (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4 are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the

  13. An improved model for studies on transdermal drug absorption invivo in rats

    NARCIS (Netherlands)

    VOLLMER, U; MULLER, BW; WILFFERT, B; Peters, Thies

    1993-01-01

    In rats, transdermal drug absorption can be studied under physiological conditions by cannulating the peripheral skin vein, draining the area of the skin which is used for drug application, and collecting the blood. This method leads to decreased blood volume, which causes a reduction in skin blood

  14. An improved model for studies on transdermal drug absorption in-vivo in rats

    NARCIS (Netherlands)

    Vollmer, U.; Muller, B.W.; Wilffert, B.; Peters, Thies

    1993-01-01

    In rats, transdermal drug absorption can be studied under physiological conditions cannulating the peripheral skin vein, draining the area of the skin which is used for drug application, and collecting the blood. This method leads to decreased blood volume, which causes a reduction in skin blood flo

  15. Improved forensic hair evidence for drugs of abuse by mass spectrometry

    NARCIS (Netherlands)

    Duvivier, W.F.

    2016-01-01

    Forensic hair analysis can be used as alternative evidence next to body fluids, and to obtain retrospective timeline information of an individual’s drug exposure. Chapter 1 describes the general concepts of drug incorporation into hair, external contamination, and the current

  16. Improved forensic hair evidence for drugs of abuse by mass spectrometry

    NARCIS (Netherlands)

    Duvivier, W.F.

    2016-01-01

    Forensic hair analysis can be used as alternative evidence next to body fluids, and to obtain retrospective timeline information of an individual’s drug exposure. Chapter 1 describes the general concepts of drug incorporation into hair, external contamination, and the current

  17. Strategies for improving adherence to antiepileptic drug treatment in people with epilepsy.

    Science.gov (United States)

    Al-Aqeel, Sinaa; Gershuni, Olga; Al-Sabhan, Jawza; Hiligsmann, Mickael

    2017-02-03

    Poor adherence to antiepileptic medication is associated with increased mortality, morbidity and healthcare costs. In this review, we focus on interventions designed and tested in randomised controlled trials and quasi-randomised controlled trials to assist people with adherence to antiepileptic medication. This is an updated version of the original Cochrane review published in the Cochrane Library, Issue 1, 2010. To determine the effectiveness of interventions aimed at improving adherence to antiepileptic medication in adults and children with epilepsy. For the latest update, on 4 February 2016 we searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 4 February 2016), CINAHL Plus (EBSCOhost 1937 to 4 February 2016), PsycINFO (EBSCOhost 1887 to 4 February 2016), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. We also searched the reference lists of relevant articles. Randomised and quasi-randomised controlled trials of adherence-enhancing interventions aimed at people with a clinical diagnosis of epilepsy (as defined in individual studies), of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting. All review authors independently assessed lists of potentially relevant citations and abstracts. At least two review authors independently extracted data and performed quality assessment of each study according to the Cochrane tool for assessing risk of bias. We graded the level of evidence for each outcome according to the GRADE working group scale.The studies differed widely according to the type of intervention and measures of adherence; therefore combining data was not appropriate. We included 12 studies reporting data on 1642 participants (intervention = 833, control = 809). Eight studies targeted adults with epilepsy, one study included participants

  18. Biological evaluation of endophytic fungus, Chaetomium globosum JN711454, as potential candidate for improving drug discovery.

    Science.gov (United States)

    Selim, Khaled A; El-Beih, Ahmed A; Abdel-Rahman, Tahany M; El-Diwany, Ahmed I

    2014-01-01

    The main objective of this research work focused on investigating the biological and chemical aspects of endophytic fungus Chaetomium globosum, for pharmaceutical purposes to improve the drug discovery process. The endophytic C. globosum was isolated from healthy leaves of Egyptian medicinal plant Adiantum capillus-veneris collected from Saint Katherine Protectorate, Sinai, Egypt. The identification of C. globosum was on the basis of classical and molecular taxonomy. Gene encoding for 18S rRNA was partially sequenced, submitted to the GenBank and got the accession number JN711454, to resolve the phylogenetic relations with fungal ancestor using phylogenetic tree. To explore the biosynthetic power of endophytic C. globosum JN711454, the fungus was cultivated over five different media, oatmeal, rice, yeast malt glucose, potato dextrose agar (PDA) and Czapek's dox media, for 3 weeks at 30 °C, followed by extraction with different solvents, ethyl acetate (EA), and methanol. The ethyl acetate extract of C. globosum cultivated on PDA medium was the most potent extract. It showed strong antioxidant activity with EC50 11.5 μg/ml, potent anticancer activity with 55 % toxicity toward HepG-2 cells at 100 μg/ml and 66 % cytotoxicity to FGC4 cells at 250 μg/ml, promising butyrylcholinesterase inhibitory activities (>85 %), and moderate antimicrobial and stopped the attachment of HSV-2 virus to VERO cells. The metabolomic profiling of PDA-EA extract using LC-MS revealed the presence of several metabolites to which the observed bioactivities could be attributed. Here we report for the first time inhibitory activity of endophytic C. globosum JN711454 secondary metabolites to butyrylcholinesterase, one of neuro hydrolase enzymes that play a major role in development of Alzheimer's disease.

  19. An injectable hybrid nanoparticle-in-oil-in-water submicron emulsion for improved delivery of poorly soluble drugs

    Science.gov (United States)

    Wang, Shuo; Wang, Hua; Liang, Wenquan; Huang, Yongzhuo

    2012-04-01

    Poor drugability problems are commonly seen in a class of chemical entities with poor solubility in water and oil, and moreover, physicochemical instability of these compounds poses extra challenges in design of dosage forms. Such problems contribute a significant high failure rate in new drug development. A hybrid nanoparicle-in-oil-in-water (N/O/W) submicron emulsion was proposed for improved delivery of poorly soluble and unstable drugs (e.g., dihydroartemisinin (DHA)). DHA is known for its potent antimalarial effect and antitumor activity. However, its insolubility and instability impose big challenges for formulations, and so far, no injectable dosage forms are clinically available yet. Therefore, an injectable DHA N/O/W system was developed. Unlike other widely-explored systems (e.g., liposomes, micelles, and emulsions), in which low drug load and only short-term storage are often found, the hybrid submicron emulsion possesses three-fold higher drug-loading capacity than the conventional O/W emulsion. Of note, it can be manufactured into a freeze-drying form and can render its storage up to 6 months even in room temperature. The in vivo studies demonstrated that the PK profiles were significantly improved, and this injectable system was effective in suppressing tumor growth. The strategy provides a useful solution to effective delivery of such a class of drugs.

  20. Improved Packing Mode of Hospital Drugs%医院药品分装方式的改进

    Institute of Scientific and Technical Information of China (English)

    鲁桂华; 王恒

    2015-01-01

    目的:改进医院药品的分装方式。方法通过手工分装方式和自动包药机分装方式,分别对10种片剂进行分装速度的比较分析。结果每月分装10种药品560袋,自动包药机比手工分装药品方式速度快,工作效率高,有效控制手工分装药品所造成的污染。结论自动包药机比手工分装药品方式提高了工作效率,降低费用,减轻了药师的工作负担,节约医院的运营成本,并能避免药品二次污染,强化了药房分装药品管理。%Objective Packing methods improve hospital drugs. Methods Through the manual packing mode and automatic medicine packaging machine packaging mode, each of the 10 tablets of the comparative analysis of packing speed. Results 10 kinds of drugs in 560 monthly packing bag, automatic medicine packaging machine packaging drug way speed than the hand, high work efficiency, effective control of pollution caused by manual containing drugs. Conclusion The automatic medicine packaging machine than the hand containing drugs method improves the work efficiency, reduce costs, reduce the burden of work of hospital pharmacists, save the operation cost, and can avoid the drug two times pollution, strengthen the management of pharmacy repack-aged drug.

  1. [Evaluation and improvement of a measure of drug name similarity, vwhtfrag, in relation to subjective similarities and experimental error rates].

    Science.gov (United States)

    Tamaki, Hirofumi; Satoh, Hiroki; Hori, Satoko; Sawada, Yasufumi

    2012-01-01

    Confusion of drug names is one of the most common causes of drug-related medical errors. A similarity measure of drug names, "vwhtfrag", was developed to discriminate whether drug name pairs are likely to cause confusion errors, and to provide information that would be helpful to avoid errors. The aim of the present study was to evaluate and improve vwhtfrag. Firstly, we evaluated the correlation of vwhtfrag with subjective similarity or error rate of drug name pairs in psychological experiments. Vwhtfrag showed a higher correlation to subjective similarity (college students: r=0.84) or error rate than did other conventional similarity measures (htco, cos1, edit). Moreover, name pairs that showed coincidences of the initial character strings had a higher subjective similarity than those which had coincidences of the end character strings and had the same vwhtfrag. Therefore, we developed a new similarity measure (vwhtfrag+), in which coincidence of initial character strings in name pairs is weighted by 1.53 times over coincidence of end character strings. Vwhtfrag+ showed a higher correlation to subjective similarity than did unmodified vwhtfrag. Further studies appear warranted to examine in detail whether vwhtfrag+ has superior ability to discriminate drug name pairs likely to cause confusion errors.

  2. Preparation and characterization of TAM-loaded HPMC/PAN composite fibers for improving drug-release profiles.

    Science.gov (United States)

    Shen, Xiaxia; Yu, Dengguang; Zhang, Xiaofei; Branford-White, Christopher; Zhu, Limin

    2011-01-01

    The present paper reports the preparation and characterization of composite hydroxypropyl methylcellulose/polyacrylonitrile (HPMC/PAN)-medicated fibers via a wet spinning technique. Tamoxifen (TAM) was selected as a model drug. Numerous analyses were conducted to characterize the mechanical, structure and morphology properties of the composite fibers. The drug content and in vitro dissolution behavior were also investigated. SEM images showed that the TAM-loaded HPMC/PAN composite fibers had a finger-like outer skin and a porous structure. FT-IR spectra demonstrated that there was a good compatibility between polymer and drug. Results from X-ray diffraction and DSC suggested that most of the incorporated TAM was evenly distributed in the fiber matrix in an amorphous state, except for a minority that aggregated on the surface of fibers. The drug content in the fibers was lower than that in the spinning solution and about 10% of TAM was lost during spinning process. In vitro dissolution results indicated that, compared to TAM-PAN fibers, HPMC/PAN composite systems had weaker initial burst release effects and more drug-loading. The combination of hydrophilic polymer HPMC with PAN could improve the performance of polymer matrix composite fibers in regulating the drug-release profiles.

  3. Improving the dissolution rate of hydrophobic drugs through encapsulation in porous lactose as a new biocompatible porous carrier.

    Science.gov (United States)

    Ebrahimi, Amirali; Saffari, Morteza; Langrish, Timothy

    2017-04-15

    T he dissolution rates of indomethacin (IMC) and nifedipine (NIF) as poorly water-soluble model drugs have been significantly improved by encapsulating their molecules in the porous structure of engineered-particles of lactose as a new biocompatible porous carrier. The formulation method used in this study utilized a template-based spray-drying technique for in-situ production of porous lactose followed by two solvent-based drug-loading methods: (i) adsorption from organic solution, and (ii) incipient wetness impregnation to incorporate the drugs inside the porous lactose. In both cases, the results of DSC and XRD have revealed the deposition of nano-sized crystals of drugs inside the nanopores due to the nanoconfinement phenomenon. Greater extents of drug loadings have been achieved during the indomethacin adsorption due to the hydrogen-bonding interaction with the surface of lactose, as determined by FTIR spectroscopy. The in vitro release studies in simulated gastric fluid (SGF) have shown faster release rates for the impregnated particles compared with drug-loaded particles via the adsorption method. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Improving the detection limits of antispasmodic drugs electrodes by using modified membrane sensors with inner solid contact.

    Science.gov (United States)

    Ibrahim, Hosny; Issa, Y M; Abu-Shawish, Hazem M

    2007-05-09

    Three coated wire electrodes (CWEs) for the antispasmodic drugs; dicyclomine (Dc), mebeverine (Mv) and drotaverine (Dv) hydrochlorides were developed. Each electrode based on ion-associate of a heteropoly anion with the drug cation incorporated in membrane sensor modified with graphite and deposited on silver internal solid contact. The influence of addition of graphite to the membranes and the type of the internal solid contact on the potentiometric responses of the electrodes was investigated. The characteristics of the new electrodes were compared to the characteristics of previously reported traditional liquid inner contact electrodes of the same drugs. The lower detection limits of the proposed electrodes were somewhat better than those observed with the corresponding liquid contact ISEs and reached (1.2-2.0)x10(-7)M. The potentiometric selectivity of the CWEs revealed a significant improvement and much faster response times compared to the liquid contact ISEs. The practical utility of each electrode has been demonstrated by using it successfully in potentiometric determination of its respective drug in pharmaceutical preparations both in batch and flow injection conditions. Each electrode was also used as an indicator electrode in the potentiometric titration of the drug against standard silicotungstic acid and in potentiometric determination of the drug concentration in urine samples.

  5. Improving Co-Amorphous Drug Formulations by the Addition of the Highly Water Soluble Amino Acid, Proline

    Directory of Open Access Journals (Sweden)

    Katrine Tarp Jensen

    2014-07-01

    Full Text Available Co-amorphous drug amino acid mixtures were previously shown to be a promising approach to create physically stable amorphous systems with the improved dissolution properties of poorly water-soluble drugs. The aim of this work was to expand the co-amorphous drug amino acid mixture approach by combining the model drug, naproxen (NAP, with an amino acid to physically stabilize the co-amorphous system (tryptophan, TRP, or arginine, ARG and a second highly soluble amino acid (proline, PRO for an additional improvement of the dissolution rate. Co-amorphous drug-amino acid blends were prepared by ball milling and investigated for solid state characteristics, stability and the dissolution rate enhancement of NAP. All co-amorphous mixtures were stable at room temperature and 40 °C for a minimum of 84 days. PRO acted as a stabilizer for the co-amorphous system, including NAP–TRP, through enhancing the molecular interactions in the form of hydrogen bonds between all three components in the mixture. A salt formation between the acidic drug, NAP, and the basic amino acid, ARG, was found in co-amorphous NAP–ARG. In comparison to crystalline NAP, binary NAP–TRP and NAP–ARG, it could be shown that the highly soluble amino acid, PRO, improved the dissolution rate of NAP from the ternary co-amorphous systems in combination with either TRP or ARG. In conclusion, both the solubility of the amino acid and potential interactions between the molecules are critical parameters to consider in the development of co-amorphous formulations.

  6. Ursodeoxycholic Acid Can Improve Liver Transaminase Quantities in Children with Anticonvulsant Drugs Hepatotoxicity: a Pilot Study.

    Directory of Open Access Journals (Sweden)

    Masoumeh Asgarshirazi

    2015-06-01

    Full Text Available The present study has been directed to investigate Ursodeoxycholic Acid (UDCA effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis. This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.

  7. Ursodeoxycholic Acid Can Improve Liver Transaminase Quantities in Children with Anticonvulsant Drugs Hepatotoxicity: a Pilot Study.

    Science.gov (United States)

    Asgarshirazi, Masoumeh; Shariat, Mamak; Dalili, Hosein; Keihanidoost, Zarrin

    2015-01-01

    The present study has been directed to investigate Ursodeoxycholic Acid (UDCA) effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis). This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.

  8. Improving access to computer-based library and drug information services in patient-care areas.

    Science.gov (United States)

    Tobia, R C; Bierschenk, N F; Knodel, L C; Bowden, V M

    1990-01-01

    A project to increase access to drug and biomedical information through electronic linkage of drug information and library services to three patient-care areas is described. In February 1987, microcomputer work stations were installed in the Bexar County Hospital District's hospital emergency department, medical residents' office, and ambulatory-care clinic, as well as in The University of Texas Health Science Center's library reference area and drug information service office. Drug information was available on compact disk through the Micromedex Computerized Clinical Information System (CCIS) database, which includes DRUGDEX, POISINDEX, EMERGINDEX, and IDENTIDEX. Each work station was also connected to the library's computer via modem, allowing access to the Library Information System, books, journals, audiovisual materials, miniMEDLINE, and an electronic mail system. During the six-month project, the system was used 5487 times by 702 people. The system was successful in providing drug and other information in clinical settings and in introducing clinical staff members to new information technology. To increase access to the system after the project ended, the CD-ROM version was discontinued, and the distributed tape version of CCIS for VAX computers was added to the library's online information system, making drug information more available throughout the campus and teaching hospitals. In 1988-89 an average of 200 people accessed the tape version of CCIS each month. Although it is difficult to replace the convenience of an onsite library, at least some drug and biomedical information needs in the clinical setting can be met through computer networking.

  9. Preparation and Characterization of Self-Microemulsifying Drug Delivery System of Olmesartan Medoxomil for Bioavailability Improvement

    Directory of Open Access Journals (Sweden)

    Shailesh T. Prajapati

    2013-01-01

    Full Text Available Olmesartan medoxomil (OLM is an angiotensin II receptor blocker (ARB antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 μg/ml. The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20 mg, Tween 80 (33%v/v, Transcutol P (33%v/v, and Acrysol EL 135 (34%v/v had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route.

  10. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-04-01

    Full Text Available Maria João Gomes,1 José das Neves,1,2 Bruno Sarmento1,2 1Instituto de Engenharia Biomédica (INEB, Porto, Portugal; 2Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal Abstract: Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood–brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood–brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. Keywords: HIV/AIDS, blood–brain barrier, protease inhibitors, efflux transporters, drug targeting

  11. Failure-mode and effects analysis in improving a drug distribution system.

    Science.gov (United States)

    McNally, K M; Page, M A; Sunderland, V B

    1997-01-15

    The medication error rate in an existing ward stock drug distribution system and in an alternative system developed after failure-mode and effects analysis (FMEA) was applied to the ward stock system was studied. In the ward stock system of a large teaching hospital in Western Australia, bulk drug packs were stored in cupboards on the wards, and drug products were transferred to drug trolleys before dose administration by nurses. A pharmacist used the disguised-observer technique to determine the error rate in the ward stock system for a medical ward and a surgical ward. The errors and each step in the system were studied by FMEA. A unit supply individual-patient dispensing (USIPD) system was formulated to respond to the failure modes identified. In this system, a five-day supply of medication was dispensed for each patient from a satellite pharmacy close to the ward. Medication charts were reviewed by a pharmacist, and drugs were dispensed in labeled vials that were placed in a locked drawer at the patient's bedside. The error rate under the USIPD system was determined. Problem areas in the ward stock system identified by FMEA included drug availability, review of orders, drug selection, patient-related issues, and use of nurses' time. The percentage of opportunities during which any error occurred was significantly lower under the USIPD system on both wards. FMEA was used to identify deficiencies in the ward stock system that led to medication errors in an Australian hospital. An alternative drug distribution system designed to address the problems identified was associated with fewer errors.

  12. Improved forensic hair evidence for drugs of abuse by mass spectrometry

    OpenAIRE

    Duvivier, W.F.

    2016-01-01

    Forensic hair analysis can be used as alternative evidence next to body fluids, and to obtain retrospective timeline information of an individual’s drug exposure. Chapter 1 describes the general concepts of drug incorporation into hair, external contamination, and the current status and limitations of hair analysis methods are introduced. Furthermore, an overview of ambient ionization techniques is given, with emphasis on direct analysis in real time (DART). The instrumentation, ionizat...

  13. Improving Protocol Design Feasibility to Drive Drug Development Economics and Performance

    OpenAIRE

    2014-01-01

    Protocol design complexity has increased substantially during the past decade and this in turn has adversely impacted drug development economics and performance. This article reviews the results of two major Tufts Center for the Study of Drug Development studies quantifying the direct cost of conducting less essential and unnecessary protocol procedures and of implementing amendments to protocol designs. Indirect costs including personnel time, work load and cycle time delays associated with ...

  14. Improving Protocol Design Feasibility to Drive Drug Development Economics and Performance

    OpenAIRE

    2014-01-01

    Protocol design complexity has increased substantially during the past decade and this in turn has adversely impacted drug development economics and performance. This article reviews the results of two major Tufts Center for the Study of Drug Development studies quantifying the direct cost of conducting less essential and unnecessary protocol procedures and of implementing amendments to protocol designs. Indirect costs including personnel time, work load and cycle time delays associated with...

  15. Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy

    Directory of Open Access Journals (Sweden)

    Fegert Jörg M

    2009-04-01

    Full Text Available Abstract Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded 1 introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents.

  16. Improving the assessment of heart toxicity for all new drugs through translational regulatory science.

    Science.gov (United States)

    Johannesen, L; Vicente, J; Gray, R A; Galeotti, L; Loring, Z; Garnett, C E; Florian, J; Ugander, M; Stockbridge, N; Strauss, D G

    2014-05-01

    Fourteen drugs have been removed from the market worldwide because they cause torsade de pointes. Most drugs that cause torsade can be identified by assessing whether they block the human ether à gogo related gene (hERG) potassium channel and prolong the QT interval on the electrocardiogram. In response, regulatory agencies require new drugs to undergo "thorough QT" studies. However, some drugs block hERG potassium channels and prolong QT with minimal torsade risk because they also block calcium and/or sodium channels. Through analysis of clinical and preclinical data from 34 studies submitted to the US Food and Drug Administration and by computer simulations, we demonstrate that by dividing the QT interval into its components of depolarization (QRS), early repolarization (J-Tpeak), and late repolarization (Tpeak-Tend), along with atrioventricular conduction delay (PR), it may be possible to determine which hERG potassium channel blockers also have calcium and/or sodium channel blocking activity. This translational regulatory science approach may enable innovative drugs that otherwise would have been labeled unsafe to come to market.

  17. Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth.

    Science.gov (United States)

    Ghosh, Indrajit; Bose, Sonali; Vippagunta, Radha; Harmon, Ferris

    2011-05-16

    The purpose of this study was to develop a nanosuspension of a poorly soluble drug by nanomilling process using wet media milling to achieve superior in vitro dissolution and high in vivo exposure in pharmacokinetic studies. A promising nanosuspension was developed with Vitamin E TPGS based formulation with particle size in the nano range. Although the formulation showed significant improvement during in vitro dissolution and in vivo plasma level, probably due to the strong hydrophobic interaction between Vitamin TPGS and the drug molecule, crystal growth was observed during stability studies. A systematic study was done with different combinations of solubilizer/stabilizer system in order to obtain a more stable nanosuspension. Hydroxypropyl methylcellulose (HPMC 3 cps) was found to stabilize the nanosuspension by better surface coverage due to stronger interaction with the drug as compared to other stabilizers used in this study.

  18. Improving the translation in Europe of nanomedicines (a.k.a. drug delivery) from academia to industry.

    Science.gov (United States)

    Eaton, Michael A W

    2012-12-28

    Over the last decade the involvement of European academic scientists in the translation of Nanomedicines and Drug Delivery into useful therapeutics has been modest. Funders have become increasingly concerned and some attempts have been made in Europe to improve impact. While the consequences are minimal at present for stakeholders, the eventual impact at national and political levels could be serious and is likely to lead to reverse innovation - the import of healthcare products from developing economies - if not addressed. Some knowledge of industrial drug development is critical for innovation in this regulated sector - this information being not easily obtained outside Pharma. While peer review has failings, more important is project inception, since once started research takes on a life of its own. This paper aims to encourage healthcare researchers to take a more translational approach to selecting (applied) drug delivery projects.

  19. A Novel Clinical Pharmacy Management System in Improving the Rational Drug Use in Department of General Surgery

    Directory of Open Access Journals (Sweden)

    L Bao

    2013-01-01

    Full Text Available Hospital information system is widely used to improve work efficiency of hospitals in China. However, it is lack of the function providing pharmaceutical information service for clinical pharmacists. A novel clinical pharmacy management system developed by our hospital was introduced to improve the work efficiency of clinical pharmacists in our hospital and to carry out large sample statistical analyzes by providing pharmacy information services and promoting rational drug use. Clinical pharmacy management system was developed according to the actual situation. Taking prescription review in the department of general surgery as the example, work efficiency of clinical pharmacists, quality and qualified rates of prescriptions before and after utilizing clinical pharmacy management system were compared. Statistics of 48,562 outpatient and 5776 inpatient prescriptions of the general surgical department were analyzed. Qualified rates of both the inpatient and outpatient prescriptions of the general surgery department increased, and the use of antibiotics decreased. This system apparently improved work efficiency, standardized the level and accuracy of drug use, which will improve the rational drug use and pharmacy information service in our hospital. Meanwhile, utilization of prophylactic antibiotics for the aseptic operations also reduced.

  20. Pulmonary administration of a doxorubicin-conjugated dendrimer enhances drug exposure to lung metastases and improves cancer therapy.

    Science.gov (United States)

    Kaminskas, Lisa M; McLeod, Victoria M; Ryan, Gemma M; Kelly, Brian D; Haynes, John M; Williamson, Mark; Thienthong, Neeranat; Owen, David J; Porter, Christopher J H

    2014-06-10

    Direct administration of chemotherapeutic drugs to the lungs significantly enhances drug exposure to lung resident cancers and may improve chemotherapy when compared to intravenous administration. Direct inhalation of uncomplexed or unencapsulated cytotoxic drugs, however, leads to bolus release and unacceptable lung toxicity. Here, we explored the utility of a 56kDa PEGylated polylysine dendrimer, conjugated to doxorubicin, to promote the controlled and prolonged exposure of lung-resident cancers to cytotoxic drug. After intratracheal instillation to rats, approximately 60% of the dendrimer was rapidly removed from the lungs (within 24h) via mucociliary clearance and absorption into the blood. This was followed by a slower clearance phase that reflected both absorption from the lungs (bioavailability 10-13%) and biodegradation of the dendrimer scaffold. After 7days, approximately 15% of the dose remained in the lungs. A syngeneic rat model of lung metastasised breast cancer was subsequently employed to compare the anticancer activity of the dendrimer with a doxorubicin solution formulation after intravenous and pulmonary administration. Twice weekly intratracheal instillation of the dendrimer led to a >95% reduction in lung tumour burden after 2weeks in comparison to IV administration of doxorubicin solution which reduced lung tumour burden by only 30-50%. Intratracheal instillation of an equivalent dose of doxorubicin solution led to extensive lung-related toxicity and death withinseveral days of a single dose. The data suggest that PEGylated dendrimers have potential as inhalable drug delivery systems to promote the prolonged exposure of lung-resident cancers to chemotherapeutic drugs and to improve anti-cancer activity.

  1. Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury.

    Science.gov (United States)

    Goldring, Christopher; Antoine, Daniel J; Bonner, Frank; Crozier, Jonathan; Denning, Chris; Fontana, Robert J; Hanley, Neil A; Hay, David C; Ingelman-Sundberg, Magnus; Juhila, Satu; Kitteringham, Neil; Silva-Lima, Beatriz; Norris, Alan; Pridgeon, Chris; Ross, James A; Young, Rowena Sison; Tagle, Danilo; Tornesi, Belen; van de Water, Bob; Weaver, Richard J; Zhang, Fang; Park, B Kevin

    2017-02-01

    Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury. Nevertheless, a single-cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (Hepatology 2017;65:710-721).

  2. Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy.

    Science.gov (United States)

    Wang, Chang-Fang; Mäkilä, Ermei M; Kaasalainen, Martti H; Hagström, Marja V; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2015-04-01

    Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry. The intracellular distribution of the MTX-PSi nanoparticles was confirmed by transmission electron microscopy. Compared to pure MTX, the MTX-PSi achieved similar inhibition of cell proliferation in folate receptor (FR) over-expressing U87 MG cancer cells, and a higher effect in low FR-expressing EA.hy926 cells. Nuclear fragmentation analysis demonstrated programmed cell apoptosis of MTX-PSi in the high/low FR-expressing cancer cells, whereas PSi alone at the same dose had a minor effect on cell apoptosis. Finally, the porous structure of MTX-PSi enabled a successful concomitant loading of another anti-angiogenic hydrophobic drug, sorafenib, and considerably enhanced the dissolution rate of sorafenib. Overall, the MTX-PSi nanoparticles can be used as a platform for combination chemotherapy by simultaneously enhancing the dissolution rate of a hydrophobic drug and sustaining the release of a conjugated chemotherapeutic drug.

  3. Polymer-Based Prodrugs: Improving Tumor Targeting and the Solubility of Small Molecule Drugs in Cancer Therapy.

    Science.gov (United States)

    Dragojevic, Sonja; Ryu, Jung Su; Raucher, Drazen

    2015-12-04

    The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy. To help circumvent problems associated with solubility, most cancer drugs are now formulated with co-solubilizers. However, these agents often also introduce severe side effects, thereby restricting effective treatment and patient quality of life. A promising approach to addressing problems in anticancer drug solubility and selectivity is their conjugation with polymeric carriers to form polymer-based prodrugs. These polymer-based prodrugs are macromolecular carriers, designed to increase the aqueous solubility of antitumor drugs, can enhance bioavailability. Additionally, polymer-based prodrugs approach exploits unique features of tumor physiology to passively facilitate intratumoral accumulation, and so improve chemodrug pharmacokinetics and pharmacological properties. This review introduces basic concepts of polymer-based prodrugs, provides an overview of currently emerging synthetic, natural, and genetically engineered polymers that now deliver anticancer drugs in preclinical or clinical trials, and highlights their major anticipated applications in anticancer therapies.

  4. Polymer-Based Prodrugs: Improving Tumor Targeting and the Solubility of Small Molecule Drugs in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Sonja Dragojevic

    2015-12-01

    Full Text Available The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy. To help circumvent problems associated with solubility, most cancer drugs are now formulated with co-solubilizers. However, these agents often also introduce severe side effects, thereby restricting effective treatment and patient quality of life. A promising approach to addressing problems in anticancer drug solubility and selectivity is their conjugation with polymeric carriers to form polymer-based prodrugs. These polymer-based prodrugs are macromolecular carriers, designed to increase the aqueous solubility of antitumor drugs, can enhance bioavailability. Additionally, polymer-based prodrugs approach exploits unique features of tumor physiology to passively facilitate intratumoral accumulation, and so improve chemodrug pharmacokinetics and pharmacological properties. This review introduces basic concepts of polymer-based prodrugs, provides an overview of currently emerging synthetic, natural, and genetically engineered polymers that now deliver anticancer drugs in preclinical or clinical trials, and highlights their major anticipated applications in anticancer therapies.

  5. Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

    Science.gov (United States)

    Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

    2016-06-01

    One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.

  6. A New Concept of a Drug Delivery System with Improved Precision and Patient Safety Features

    Directory of Open Access Journals (Sweden)

    Florian Thoma

    2014-12-01

    Full Text Available This paper presents a novel dosing concept for drug delivery based on a peristaltic piezo-electrically actuated micro membrane pump. The design of the silicon micropump itself is straight-forward, using two piezoelectrically actuated membrane valves as inlet and outlet, and a pump chamber with a piezoelectrically actuated pump membrane in-between. To achieve a precise dosing, this micropump is used to fill a metering unit placed at its outlet. In the final design this metering unit will be made from a piezoelectrically actuated inlet valve, a storage chamber with an elastic cover membrane and a piezoelectrically actuated outlet valve, which are connected in series. During a dosing cycle the metering unit is used to adjust the drug volume to be dispensed before delivery and to control the actually dispensed volume. To simulate the new drug delivery concept, a lumped parameter model has been developed to find the decisive design parameters. With the knowledge taken from the model a drug delivery system is designed that includes a silicon micro pump and, in a first step, a silicon chip with the storage chamber and two commercial microvalves as a metering unit. The lumped parameter model is capable to simulate the maximum flow, the frequency response created by the micropump, and also the delivered volume of the drug delivery system.

  7. The effect of HPMCAS functional groups on drug crystallization from the supersaturated state and dissolution improvement.

    Science.gov (United States)

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2014-04-10

    The inhibitory effect on drug crystallization in aqueous solution was evaluated using various forms of hydroxypropyl methylcellulose acetate succinate (HPMCAS). HPMCAS suppressed crystallization of carbamazepine (CBZ), nifedipine (NIF), mefenamic acid, and dexamethasone. The inhibition of drug crystallization mainly derived from molecular level hydrophobic interactions between the drug and HPMCAS. HPMCAS with a lower succinoyl substituent ratio strongly suppressed drug crystallization. The inhibition of crystallization was affected by pH, with the CBZ crystallization being inhibited at a higher pH due to the hydrophilization of HPMCAS derived from succinoyl ionization. The molecular mobility of CBZ in an HPMCAS solution was evaluated by 1D-(1)H NMR and relaxation time measurements. CBZ mobility was strongly suppressed in the HPMCAS solutions where strong inhibitory effects on CBZ crystallization were observed. The mobility suppression of CBZ in the HPMCAS solution was derived from intermolecular interactions between CBZ and HPMCAS leading to an inhibition of crystallization. The effect of HPMCAS on the drug dissolution rate was evaluated using an NIF/HPMCAS solid dispersion. The dissolution rate of NIF was increased when HPMCAS with a higher succinoyl substituent ratio was used.

  8. Nanoparticle Drug Loading as a Design Parameter to Improve Docetaxel Pharmacokinetics and Efficacy

    Science.gov (United States)

    Chu, Kevin S.; Schorzman, Allison N.; Finniss, Mathew C.; Bowerman, Charles J.; Peng, Lei; Luft, J. Christopher; Madden, Andrew; Wang, Andrew Z.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel. PMID:23899444

  9. Improved management of drugs, hormones and pesticides in Africa : policy and trade issues

    Directory of Open Access Journals (Sweden)

    E.S. Mitema

    2009-09-01

    Full Text Available Drugs, hormones and pesticides are chemical compounds used for alleviation of various diseases in animals. There are many classes of drugs which have been used and in the case of natural steroid hormones these have been used to increase mass gain by stimulating protein anabolism. Pesticides have been used for many years in the control of ectoparasites which transmit important human and livestock diseases. The purpose of the present article is to review procedures for management of veterinary products to facilitate national and international trade.

  10. Improving the prediction of the brain disposition for orally administered drugs using BDDCS

    DEFF Research Database (Denmark)

    Broccatelli, Fabio; Larregieu, Caroline A.; Cruciani, Gabriele;

    2012-01-01

    In modeling blood–brain barrier (BBB) passage, in silico models have yielded ~80% prediction accuracy, and are currently used in early drug discovery. Being derived from molecular structural information only, these models do not take into account the biological factors responsible for the in vivo...... were found to markedly distribute throughout the brain; this includes a number of BDDCS class 1 drugs shown to be Pgp substrates. This new perspective provides a further interpretation of how Pgp influences the sedative effects of H1-histamine receptor antagonists.......In modeling blood–brain barrier (BBB) passage, in silico models have yielded ~80% prediction accuracy, and are currently used in early drug discovery. Being derived from molecular structural information only, these models do not take into account the biological factors responsible for the in vivo...... outcome. Passive permeability and P-glycoprotein (Pgp, ABCB1) efflux have been successfully recognized to impact xenobiotic extrusion from the brain, as Pgp is known to play a role in limiting the BBB penetration of oral drugs in humans. However, these two properties alone fail to explain the BBB...

  11. Medicinal chemistry based approaches and nanotechnology-based systems to improve CNS drug targeting and delivery.

    Science.gov (United States)

    Vlieghe, Patrick; Khrestchatisky, Michel

    2013-05-01

    The central nervous system (CNS) is protected by various barriers, which regulate nervous tissue homeostasis and control the selective and specific uptake, efflux, and metabolism of endogenous and exogenous molecules. Among these barriers is the blood-brain barrier (BBB), a physical and physiological barrier that filters very efficiently and selectively the entry of compounds from the blood to the brain and protects nervous tissue from harmful substances and infectious agents present in the bloodstream. The BBB also prevents the entry of potential drugs. As a result, various drug targeting and delivery strategies are currently being developed to enhance the transport of drugs from the blood to the brain. Following a general introduction, we briefly overview in this review article the fundamental physiological properties of the BBB. Then, we describe current strategies to bypass the BBB (i.e., invasive methods, alternative approaches, and temporary opening) and to cross it (i.e., noninvasive approaches). This section is followed by a chapter addressing the chemical and technological solutions developed to cross the BBB. A special emphasis is given to prodrug-targeting approaches and targeted nanotechnology-based systems, two promising strategies for BBB targeting and delivery of drugs to the brain.

  12. Endophytes : exploiting biodiversity for the improvement of natural product-based drug discovery

    NARCIS (Netherlands)

    Staniek, Agata; Woerdenbag, Herman J.; Kayser, Oliver

    2008-01-01

    Endophytes, microorganisms that colonize internal tissues of all plant species, create a huge biodiversity with yet unknown novel natural products, presumed to push forward the frontiers of drug discovery. Next to the clinically acknowledged antineoplastic agent, paclitaxel, endophyte research has y

  13. Endophytes : exploiting biodiversity for the improvement of natural product-based drug discovery

    NARCIS (Netherlands)

    Staniek, Agata; Woerdenbag, Herman J.; Kayser, Oliver

    2008-01-01

    Endophytes, microorganisms that colonize internal tissues of all plant species, create a huge biodiversity with yet unknown novel natural products, presumed to push forward the frontiers of drug discovery. Next to the clinically acknowledged antineoplastic agent, paclitaxel, endophyte research has y

  14. A Patient Education Program to Improve Adherence Rates with Antituberculosis Drug Regimens.

    Science.gov (United States)

    Morisky, Donald E.; And Others

    1990-01-01

    An incentive scheme to reward positive health behaviors (adherence to antituberculosis drug regimens) was tested with 88 active and 117 preventive patients randomly assigned to intervention and control groups. Preventive patients who received incentives were significantly more likely to continue care and had higher adherence levels. Actives showed…

  15. Improvement of drug exposure data in a registration of congenital abnormalities

    DEFF Research Database (Denmark)

    de Jong van den Berg, L; Feenstra, N; Sørensen, Henrik Toft;

    1999-01-01

    for the registration of birth defects, filled out by physicians or midwives since 1981. Furthermore, hospital records are used and general practitioners are asked to add information on drug use. The present pilot study used pharmacy records and maternal questionnaires as well as maternal interview data to complete...

  16. How can we improve the pre-clinical development of drugs for stroke?

    NARCIS (Netherlands)

    Sena, Emily; van der Worp, H. Bart; Howells, David; Macleod, Malcolm

    2007-01-01

    The development of stroke drugs has been characterized by success in animal studies and subsequent failure in clinical trials. Animal studies might have overstated efficacy, or clinical trials might have understated efficacy; in either case we need to better understand the reasons for failure. Techn

  17. Biomimickry of UPEC Cytoinvasion: A Novel Concept for Improved Drug Delivery in UTI.

    Science.gov (United States)

    Pichl, Clara Maria; Dunkl, Bernhard; Brauner, Bernhard; Gabor, Franz; Wirth, Michael; Neutsch, Lukas

    2016-02-04

    Urinary tract infections (UTIs) are among the most common bacterial infections. In an increasing number of cases, pathogen (multi-)resistance hampers durable treatment success via the standard therapies. On the functional level, the activity of urinary excreted antibiotics is compromized by the efficient tissue colonization mechanism of uropathogenic Escherichia coli (UPEC). Advanced drug delivery systems aim at exploiting a glycan-mediated targeting mechanism, similar to the UPEC invasion pathway, to increase bioavailability. This may be realized by conjugation of intravesically applied drugs or drug carriers to chosen plant lectins. Higher local drug concentrations in or nearby bacterial reservoirs may be gained, with higher chances for complete eradication. In this study, preliminary parameters to clarify the potential of this biorecognitive approach were evaluated. Glycan-triggered interaction cascades and uptake processes of several plant lectins with distinct carbohydrate specificities were characterized, and wheat germ agglutinin (WGA) could be identified as the most promising targeter for crossing the urothelial membrane barrier. In partially differentiated primary cells, intracellular accumulation sites were largely identical for GlcNAc- and Mannose-specific lectins. This indicates that WGA-mediated delivery may also enter host cells via the FimH-dependent uptake pathway.

  18. Folic Acid-Chitosan Conjugated Nanoparticles for Improving Tumor-Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Huijuan Song

    2013-01-01

    Full Text Available Objective. To prepare folic acid-chitosan conjugated nanoparticles (FA-CS NPs and evaluate their targeting specificity on tumor cells. Methods. Chitosan (CS NPs were prepared by ionic cross linking method, and folic acid (FA was conjugated with CS NPs by electrostatic interaction. The properties of NPs were investigated, and doxorubicin hydrochloride (Dox as a model drug was encapsulated for investigating drug release pattern in vitro. The cytotoxicity and cellular uptake of FA-CS NPs were also investigated. Results. The results reveal that the obtained FA-CS NPs were monodisperse nanoparticles with suitable average size and positive surface charge. Dox was easily loaded into FA-CS NPs, and the release pattern showed a long and biphasic drug release. Noticeable phagocytosis effect was observed in the presence of rhodamine B-labeled FA-CSNPs when incubating with the folate receptor-positive SMMC-7221 cells. Conclusion. Compared with the unmodified CS NPs, FA-CS NPs showed much higher cell uptaking ability due to the known folate-receptor mediated endocytosis. FA-CS NPs provide a potential way to enhance the using efficiency of antitumor drug by folate receptor mediated targeting delivery.

  19. QbD-Oriented Development of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) of Valsartan with Improved Biopharmaceutical Performance.

    Science.gov (United States)

    Bandyopadhyay, Shantanu; Beg, Sarwar; Katare, O P; Sharma, Gajanand; Singh, Bhupinder

    2015-01-01

    The objectives of the present studies were to develop the systematically optimized selfnanoemulsifying drug delivery systems (SNEDDS) of valsartan employing the holistic QbD approach. The quality profile target product (QTPP) was defined and critical quality attributes (CQAs) earmarked. Preformulation studies including the equilibrium solubility and pseudoternary phase titration studies facilitated the selection of suitable lipids and emulgents for formulation of SNEDDS. Risk assessment and factor screening studies facilitated the selection of Lauroglycol FCC and Capmul MCM L8 (i.e., lipid), Tween 40 and Tween 80 (i.e., emulgent) as the critical material attributes (CMAs) for SNEDDS prepared using medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs). A central composite design (CCD) was employed for systematic optimization of SNEDDS, taking globule size (Dnm), drug release in 10 min (Q10min) and amount permeated in 45 min (%Perm45min) as the CQAs. Design space was generated using apt mathematical models to embark upon the optimized formulations and validation of the QbD. In situ SPIP studies revealed significant improvement in the absorptivity and permeability parameters of SNEDDS owing to the inhibition of P-gp/MRP2 efflux vis-à-vis the conventional marketed formulation and pure drug. In vivo pharmacokinetic studies corroborated marked enhancement in the oral bioavailability drug from SNEDDS vis-à-vis the marketed formulation. Establishment of various levels of in vitro/in vivo correlations (IVIVC) indicated excellent goodness of fit between the in vitro drug release data with the in vivo absorption parameters. In a nutshell, the present studies report successful QbD-based development of MCT and LCT-SNEDDS of valsartan with improved biopharmaceutical performance.

  20. Stem cell-derived models to improve mechanistic understanding and prediction of human drug induced liver injury

    Science.gov (United States)

    Goldring, Christopher; Antoine, Daniel J.; Bonner, Frank; Crozier, Jonathan; Denning, Chris; Fontana, Robert J.; Hanley, Neil A.; Hay, David C.; Ingelman-Sundberg, Magnus; Juhila, Satu; Kitteringham, Neil; Silva-Lima, Beatriz; Norris, Alan; Pridgeon, Chris; Ross, James A.; Sison Young, Rowena; Tagle, Danilo; Tornesi, Belen; van de Water, Bob; Weaver, Richard J.; Zhang, Fang; Park, B. Kevin

    2016-01-01

    Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalised toxicology to determine inter-individual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury (DILI) means that no current single cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human DILI. Nevertheless, a single cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment, and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally-differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. PMID:27775817

  1. Drug discovery and beyond: the role of public-private partnerships in improving access to new malaria medicines.

    Science.gov (United States)

    Nwaka, Solomon

    2005-10-01

    Traditional pharmaceutical research and development (R&D) strategy has failed to address the desperate need for new antimalarial drugs. The populations affected are too poor to attract commercially-driven R&D. Over the last few years, a new model, the public-private partnership for product development, has radically changed the antimalarial R&D landscape. The partnerships bring together academic and industry expertise with funding from governmental, philanthropic and charitable sources. The Medicines for Malaria Venture, a not-for-profit foundation based in Geneva, aims to develop new antimalarials for developing countries through public-private partnership. It is currently managing a portfolio of around 20 projects at various stages of development. However, as in all drug R&D, some of these projects will fail. The portfolio approach helps to maximize the chances of success, but there are obvious challenges, including financial and managerial ones. Proactive management of the two vital interfaces in the drug supply chain is important for success. Upstream, basic research must be aligned with translational research in order to ensure a continuous supply of leads into the development pipeline. Meanwhile, downstream, drug discovery and development must be aligned with access to ensure optimal health impact. All stages require partnership, sustainable financing and the engagement of disease-endemic countries. The recent G8 report on Africa has lent support to mechanisms aimed at improving health and achieving the Millenium Development Goals.

  2. Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Rao S

    2011-06-01

    Full Text Available Shasha Rao, Yunmei Song, Frank Peddie, Allan M EvansSansom Institute for Health Research, Division of Health Sciences, University of South Australia, Adelaide, South Australia, AustraliaAbstract: Poorly water-soluble drugs, such as phenylephrine, offer challenging problems for buccal drug delivery. In order to overcome these problems, particle size reduction (to the nanometer range and cyclodextrin complexation were investigated for permeability enhancement. The apparent solubility in water and the buccal permeation of the original phenylephrine coarse powder, a phenylephrine–cyclodextrin complex and phenylephrine nanosuspensions were ­characterized. The particle size and particle surface properties of phenylephrine nanosuspensions were used to optimize the size reduction process. The optimized phenylephrine nanosuspension was then freeze dried and incorporated into a multi-layered buccal patch, consisting of a small tablet adhered to a mucoadhesive film, yielding a phenylephrine buccal product with good dosage accuracy and improved mucosal permeability. The design of the buccal patch allows for drug incorporation without the need to change the mucoadhesive component, and is potentially suited to a range of poorly water-soluble compounds.Keywords: buccal drug delivery, nanosuspension, solubility, permeation enhancement, mucoadhesion

  3. Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives.

    Science.gov (United States)

    Xie, Tian; Taylor, Lynne S

    2016-03-07

    Amorphous solid dispersions (ASDs) have been extensively exploited as a strategy for improving the dissolution performance of poorly water-soluble drugs. However, factors underpinning the observed dissolution profiles are not clearly understood, and the choice of polymeric carriers is largely empirical. In the current study, the dissolution performance of a high drug loading ASD containing the poorly water-soluble, anti-inflammatory agent, celecoxib, was optimized by using binary polymers combinations. Polyacrylic acid (PAA), a highly water-soluble polymer, was used to substantially increase the dissolution rate of the drug, while hydroxypropyl methyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS) were added to stabilize the solid amorphous matrix against crystallization upon hydration, as well as to maintain supersaturation. Quantitative measurements of the impact of the polymers on the solution nucleation and growth rates of celecoxib revealed that, while the cellulose derivatives are effective nucleation inhibitors, it is more difficult to completely prevent crystal growth in solutions containing seed crystals, in particular at high supersaturations. Therefore, it is critical to prevent the formation of crystals in the dissolving matrix during dissolution. By using certain ratios of HPMC and PAA, both rapid release as well as crystallization inhibition could be achieved, even at high drug loadings. Utilizing combinations of polymers may therefore be useful to tailor release profiles while providing optimized crystallization inhibition.

  4. Dissolution improvement of solid self-emulsifying drug delivery systems of fenofi brate using an inorganic high surface adsorption material

    Directory of Open Access Journals (Sweden)

    Shazly Gamal

    2015-03-01

    Full Text Available Solidification of lipid formulations using adsorbents is a recent technique attracting great interest due to its favourable properties including flexibility in dose division, reduction of intra-subject and inter-subject variability, improvement in efficacy/safety profile and enhancement of physical/ chemical stability. The current study aims to convert liquid self-emulsifying/nanoemulsifying drug delivery systems (SEDDS/SNEDDS into solid SEDDS/SNEDDS and to assess how adsorption of the drug onto an inorganic high surface area material, NeusilinR grade US2 (NUS2, affects its in vitro dissolution performance. Lipid formulation classification systems (LFCS Type III formulations were designed for the model anti-cholesterol drug fenofibrate. NUS2 was used to solidify the SEDDS/SNEDDS. Particle size and SEM analyses of solid SEDDS/SNEDDS powder were carried out to investigate the adsorption efficiency. In vitro dissolution studies were conducted to compare the developed formulations with the marketed product. The results of characterization studies showed that the use of 50 % (m/m adsorbent resulted in superior flowability and kept the drug stable is amorphous state. Dissolution studies allow the conclusion that the formulation containing a surfactant of higher water solubility (particularly, Type IIIB SNEDDS has comparably faster and higher release profiles than Type IIIA (SEDDS and marketed product

  5. Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review

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    Shihong Chen

    2014-01-01

    Full Text Available Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer.

  6. [Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].

    Science.gov (United States)

    Korenaga, Masaaki; Kawaguchi, Koutaro; Korenaga, Keiko; Uchida, Kouichi; Sakaida, Iso

    2006-06-01

    Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.

  7. A new cyclopamine glucuronide prodrug with improved kinetics of drug release.

    Science.gov (United States)

    Renoux, Brigitte; Legigan, Thibaut; Bensalma, Souheyla; Chadéneau, Corinne; Muller, Jean-Marc; Papot, Sébastien

    2011-12-21

    We prepared a new glucuronide prodrug of cyclopamine designed to target selectively the Hedgehog signalling pathway of cancer cells. This prodrug includes a novel self-immolative linker bearing a hydrophilic side chain that can be easily introduced via"click chemistry". With this design, the prodrug exhibits reduced toxicity compared to the free drug on U87 glioblastoma cells. However, in the presence of β-glucuronidase, the prodrug conducts to the quick release of cyclopamine thereby restoring its antiproliferative activity.

  8. Natural products to improve quality of life targeting for colon drug delivery.

    Science.gov (United States)

    Kim, Hyunjo

    2012-03-01

    The colon is largely being investigated as a site for administration of protein and peptides, which are degraded by digestive enzymes in the upper GIT. Also for local diseases of the colon such as inflammatory bowel disease, colorectal cancer and ameobiasis, drug administration to the site of action can not only reduce the dose to be administered, but also decrease the side effects. Inflammatory Bowel Disease (IBD) such as Ulcerative colitis and Crohn's disease are characterized by chronic intestinal inflammation. Intestinal bacteria initiate the activation of intestinal inflammatory processes, which are mediated by pro-inflammatory cytokines and chemokine. Increased chemokine expression has also been observed in epithelial cells, endothelial cells, and smooth muscle cells. Future trials of specific agents capable of inhibiting chemokine synthesis and secretion or blocking chemokine-chemokine receptor interaction will be important to study in patients with ulcerative colitis and Crohn's disease. Many important bioactive compounds have been discovered from natural sources using bioactivity directed fractionation and isolation (BDFl) Continuing discovery has also been facilitated by the recent development of new bioassay methods. These bioactive compounds are mostly plant secondary metabolites, and many naturally occurring pure compounds have become medicines, dietary supplements, and other useful commercial products. The present review includes various approaches investigated for colon drug delivery and their site specificity. To achieve successful colonic delivery, a drug needs to be protected from absorption and the environment of the upper gastrointestinal tract and then be abruptly released into the proximal colon, which is considered the optimum site for colon targeted delivery of drugs.

  9. Mixed micelles loaded with silybin-polyene phosphatidylcholine complex improve drug solubility

    Institute of Scientific and Technical Information of China (English)

    Rui-ling DUAN; Xun SUN; Jie LIU; Tao GONG; Zhi-rong ZHANG

    2011-01-01

    Aim: To prepare a novel formulation of phosphatidylcholine(PC)-bile salts(BS)-mixed micelles(MMs)loaded with silybin(SLB)-PC complex for parenteral applications.Methods: SLB-PC-BS-MMs were prepared using the co-precipitation method.Differential scanning calorimetry(DSC)analysis was used to confirm the formation of the complex and several parameters were optimized to obtain a high quality formulation.The water-solubility,drug loading,particle siz,zeta potential,morphology and in vivo properties of the SLB-PC-BS-MMs were determined.Results: The solubility of SLB in water was increased from 40.83±1.18 μg/mL to 10.14±0.36 mg/mL with a high drug loading(DL)of 14.43%±0.44% under optimized conditions.The SLB-PC-BS-MMs were observed by transmission electron microscopy(TEM)and scanning electron microscopy(SEM)and showed spherical shapes.The particle size and zeta potential,as measured by photon correlation spectroscopy(PCS),were about 30±4.8 nm and-39±5.0 mV,respectively.In vivo studies showed that incorporation of the SLB-PC complex into PC-BS-MMs led to a prolonged circulation time of the drug.Conclusion: This novel formulation appears to be a good candidate for drug substances that exhibit poor solubility for parenteral administration.

  10. Using the level of Service Inventory-Revised to improve assessment and treatment in drug court.

    Science.gov (United States)

    Guastaferro, Wendy P

    2012-08-01

    More than 2,000 drug courts in the United States provide supervision and substance-abuse treatment to thousands of offenders. Yet the treatment continuum from assessment to aftercare is underexplored. The effectiveness of the Level of Service Inventory-Revised (LSI-R) as a risk assessment tool is well established. However, fewer studies have considered its use in guiding treatment strategies. In using the LSI-R, the drug court program relied on the structured interview protocol (not the risk classification scores) to identify criminogenic needs that then helped determine placement in a high- or low-needs treatment track. To evaluate the effectiveness of these treatment placement decisions, this research used the LSI-R scores to examine individual and group differences (N = 182). Significant and substantive differences at the individual and group levels were found thus providing empirical support for using the LSI-R as a link between assessment and treatment. Implications for developing standards and practice protocols for drug courts are discussed.

  11. Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza

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    Xiaolin Bi

    2016-04-01

    Full Text Available The active ingredients of salvia (dried root of Salvia miltiorrhiza include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I and hydrophilic (e.g., danshensu and salvianolic acid B constituents. The low oral bioavailability of these constituents may limit their efficacy. A solid self-microemulsifying drug delivery system (S-SMEDDS was developed to load the various active constituents of salvia into a single drug delivery system and improve their oral bioavailability. A prototype SMEDDS was designed using solubility studies and phase diagram construction, and characterized by self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. Furthermore, the S-SMEDDS was prepared by dispersing liquid SMEDDS containing liposoluble extract into a solution containing aqueous extract and hydrophilic polymer, and then freeze-drying. In vitro release of tanshinone IIA, salvianolic acid B, cryptotanshinone and danshensu from the S-SMEDDS was examined, showing approximately 60%–80% of each active component was released from the S-SMEDDS in vitro within 20 min. In vivo bioavailability of these four constituents indicated that the S-SMEDDS showed superior in vivo oral absorption to a drug suspension after oral administration in rats. It can be concluded that the novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of both lipophilic and hydrophilic constituents of salvia. Thus, the S-SMEDDS can be regarded as a promising new method by which to deliver salvia extract, and potentially other multicomponent drugs, by the oral route.

  12. Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza.

    Science.gov (United States)

    Bi, Xiaolin; Liu, Xuan; Di, Liuqing; Zu, Qiang

    2016-04-08

    The active ingredients of salvia (dried root of Salvia miltiorrhiza) include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I) and hydrophilic (e.g., danshensu and salvianolic acid B) constituents. The low oral bioavailability of these constituents may limit their efficacy. A solid self-microemulsifying drug delivery system (S-SMEDDS) was developed to load the various active constituents of salvia into a single drug delivery system and improve their oral bioavailability. A prototype SMEDDS was designed using solubility studies and phase diagram construction, and characterized by self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. Furthermore, the S-SMEDDS was prepared by dispersing liquid SMEDDS containing liposoluble extract into a solution containing aqueous extract and hydrophilic polymer, and then freeze-drying. In vitro release of tanshinone IIA, salvianolic acid B, cryptotanshinone and danshensu from the S-SMEDDS was examined, showing approximately 60%-80% of each active component was released from the S-SMEDDS in vitro within 20 min. In vivo bioavailability of these four constituents indicated that the S-SMEDDS showed superior in vivo oral absorption to a drug suspension after oral administration in rats. It can be concluded that the novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of both lipophilic and hydrophilic constituents of salvia. Thus, the S-SMEDDS can be regarded as a promising new method by which to deliver salvia extract, and potentially other multicomponent drugs, by the oral route.

  13. Higher magnitude cash payments improve research follow-up rates without increasing drug use or perceived coercion.

    Science.gov (United States)

    Festinger, David S; Marlowe, Douglas B; Dugosh, Karen L; Croft, Jason R; Arabia, Patricia L

    2008-07-01

    In a prior study [Festinger, D.S., Marlowe, D.B., Croft, J.R., Dugosh, K.L., Mastro, N.K., Lee, P.A., DeMatteo, D.S., Patapis, N.S., 2005. Do research payments precipitate drug use or coerce participation? Drug Alcohol Depend. 78 (3) 275-281] we found that neither the mode (cash vs. gift card) nor magnitude ($10, $40, or $70) of research follow-up payments increased rates of new drug use or perceptions of coercion. However, higher payments and payments in cash were associated with better follow-up attendance, reduced tracking efforts, and improved participant satisfaction with the study. The present study extended those findings to higher payment magnitudes. Participants from an urban outpatient substance abuse treatment program were randomly assigned to receive $70, $100, $130, or $160 in either cash or a gift card for completing a follow-up assessment at 6 months post-admission (n congruent with 50 per cell). Apart from the payment incentives, all participants received a standardized, minimal platform of follow-up efforts. Findings revealed that neither the magnitude nor mode of payment had a significant effect on new drug use or perceived coercion. Consistent with our previous findings, higher payments and cash payments resulted in significantly higher follow-up rates and fewer tracking calls. In addition participants receiving cash vs. gift cards were more likely to use their payments for essential, non-luxury purchases. Follow-up rates for participants receiving cash payments of $100, $130, and $160 approached or exceeded the FDA required minimum of 70% for studies to be considered in evaluations of new medications. This suggests that the use of higher magnitude payments and cash payments may be effective strategies for obtaining more representative follow-up samples without increasing new drug use or perceptions of coercion.

  14. Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems.

    Science.gov (United States)

    Attama, A A; Schicke, B C; Müller-Goymann, C C

    2006-11-01

    There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application. It is line with this that this research was embarked upon to characterize mixtures of beeswax and theobroma oil with a view to applying their admixtures in drug delivery systems such as solid lipid nanoparticles and nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The admixtures were analyzed by differential scanning calorimetry (DSC), small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal heat conduction microcalorimetry (IMC). The melting behavior and microstructures of the lipid admixtures were monitored by polarized light microscopy (PLM). Transmission electron microscopy (TEM) was used to study the internal structures of the lipid bases. DSC traces indicated that the higher melting peaks were roughly constant for the different admixtures, but lower melting peaks significantly increased (p beeswax in all the lipid matrix admixtures at all stages of the study. PLM micrographs revealed differences with regard to the thermal and optical behaviors depending on the composition of the matrix. The lipid matrix consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks of isothermal storage. Crystallization exotherms of lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed change in modification after 30 min with the latter having a greater time-dependent crystallization. Generally, low non-integral Avrami exponents and growth rate constants were obtained for all the lipid matrices, with the admixture

  15. Joint medicine-information and pharmacovigilance services could improve detection and communication about drug-safety problems

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    Schjøtt J

    2014-07-01

    Full Text Available Jan Schjøtt,1–3 Jenny Bergman3 1Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, 2Institute of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, 3Regional Medicines Information and Pharmacovigilance Centre (RELIS Vest, Haukeland University Hospital, Bergen, Norway Background: RELIS is a Norwegian network of four regional medicine-information and pharmacovigilance centers where pharmacists and clinical pharmacologists provide feedback to health care professionals in spontaneous drug-related questions and adverse drug-reaction (ADR reports published in a question–answer pair (QAP database (the RELIS database and the Norwegian ADR database, respectively. Objective: To describe the potential of RELIS's dual service to improve detection and communication of drug-safety problems. Materials and methods: We searched the RELIS database for QAPs about ADRs with use of the Norwegian ADR database as a reference. We also searched the Norwegian ADR database for reports that used the RELIS database as a reference. Both searches were limited to the years 2003–2012. We then selected the example of pregabalin and drug abuse after the marketing of Lyrica in Norway in September 2004 to illustrate RELIS's potential to detect new drug-safety information through a limited number of QAPs and ADR reports. Results: A total of 5,427 (26% of 21,071 QAPs in the RELIS database concerned ADRs. QAPs from this database were used as references in 791 (4% of a total of 22,090 reports in the Norwegian ADR database. The Norwegian ADR database was used as a reference in 363 (7% of 5,427 QAPs that concerned ADRs. Between September 2004 and September 2008, RELIS received eleven questions and 13 ADR reports about suspicion of Lyrica (pregabalin and different aspects of abuse. Conclusion: RELIS processes data through two databases that facilitate communication about ADRs. Our service also has the

  16. Software-As-A-Service for improving Drug Research towards a standardized approach

    Directory of Open Access Journals (Sweden)

    Keis Husein

    2016-01-01

    Full Text Available Software as a Service (SaaS is one of the most interesting applications of a service-oriented architecture. SaaS spares users the cost of acquiring and maintaining hardware and software. The SaaS business model is very widely appreciated in the economy, because it brings not only financial benefits but also process-optimizing benefits. Drug research is a lengthy, complex and costly process that involves a number of disciplines, from medicine through economics to natural science. Until recently, the standard programs and infrastructure used for data analysis were almost exclusively commercial, proprietary, closed source and expensive. One of the major attractions of the open-source model is to customize the platform to suite the requirements and react faster on changes. There are different proprietary approaches. However there is a gap in knowledge regarding using closed and proprietary infrastructure. The aim of this research is to investigate the impact of an open source SaaS approach on the drug research process.

  17. Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake.

    Science.gov (United States)

    Luo, Yangchao; Teng, Zi; Li, Ying; Wang, Qin

    2015-05-20

    The poor stability of solid lipid nanoparticles (SLN) under acidic condition resulted in large aggregation in gastric environment, limiting their application as oral delivery systems. In this study, a series of SLN was prepared to investigate the effects of surfactant/cosurfactant and chitosan coating on their physicochemical properties as well as cellular uptake. SLN was prepared from Compritol 888 ATO using a low-energy method combining the solvent-diffusion and hot homogenization technique. Poloxamer 188 and polyethylene glycol (PEG) were effective emulsifiers to produce SLN with better physicochemical properties than SLN control. Chitosan-coated SLN exhibited the best stability under acidic condition by forming a thick layer around the lipid core, as clearly observed by transmission electron microscope. The intermolecular interactions in different formulations were monitored by Fourier transform infrared spectroscopy. Chitosan coating also significantly improved the mucoadhesive property of SLN as determined by Quartz Crystal Microbalance. In vitro drug delivery assays, cytotoxicity, and cellular uptake of SLN were studied by incorporating coumarin 6 as a fluorescence probe. Overall, chitosan-coated SLN was superior to other formulations and held promising features for its application as a potential oral drug delivery system for hydrophobic drugs.

  18. Improved dissolution rate of poorly soluble drug by incorporation of buffers.

    Science.gov (United States)

    Preechagoon, D; Udomprateep, A; Manwiwattanagul, G

    2000-08-01

    This study focused on comparing dissolution rates of indomethacin after co-compressing with three different buffers (calcium carbonate, sodium carbonate, and sodium citrate) at pH 2 and 7. Factors affecting the dissolution rate were also examined, such as type and particle size of buffer and weight-to-weight ratio of drug to buffer. It was found that, at pH 7, the release rates of indomethacin with sodium carbonate (tablets using a tableting machine, the release rates of indomethacin for the control, sodium carbonate incorporated (25% and 75% buffer loading), and sodium citrate incorporated (75% buffer loading) at a 15-min test time were 50%, 90%, 66%, and 67%, respectively.

  19. Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

    Directory of Open Access Journals (Sweden)

    Janisse Crestani de Miranda

    2011-12-01

    Full Text Available Cyclodextrins (CDs are cyclic oligosaccharides composed of D-glucopyranoside units linked by glycosidic bonds. Their main property is the ability to modify the physicochemical and biological characteristics of low-soluble drugs through the formation of drug:CD inclusion complexes. Inclusion complexation requires that host molecules fit completely or partially within the CD cavity. This adjustment is directly related to the physicochemical properties of the guest and host molecules, easy accommodation of guest molecules within the CD cavity, stoichiometry, therapeutic dose, and toxicity. However, dosage forms may achieve a high volume, depending on the amount of CD required. Thus, it is necessary to increase solubilization efficiency in order to use smaller amounts of CD. This can be achieved by adding small amounts of water-soluble polymers to the system. This review addresses aspects related to drug complexation with CDs using water-soluble polymers to optimize the amount of CD used in the formulation in order to increase drug solubility and reduce dosage form volume.Ciclodextrinas (CDs são oligossacarídeos cíclicos, compostos por unidades D-glicopiranosídicas ligadas entre si por meio de ligações glicosídicas e sua principal propriedade está na capacidade de alterar as características físico-químicas e biológicas de fármacos com baixa solubilidade por meio da formação de complexos de inclusão fármaco:CD. Para a formação dos complexos de inclusão a molécula hospedeira necessita ajustar-se total ou parcialmente no interior da cavidade da CD, onde este ajuste está diretamente ligado a propriedades físico-químicas da molécula hóspede e hospedeira, facilidade de alojamento da molécula hóspede no interior da cavidade da CD, estequiometria, dose terapêutica e toxicidade. No entanto, as formas farmacêuticas podem atingir um elevado volume, em função da quantidade de CD requerida, sendo necessário aumentar sua efici

  20. Novel designed polyoxyethylene nonionic surfactant with improved safety and efficiency for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Li C

    2014-04-01

    Full Text Available Chang Li,1 Chunmeng Sun,1 Shasha Li,1 Peng Han,2 Huimin Sun,3 Ammar Ouahab,1 Yan Shen,1 Yourui Xu,1 Yerong Xiong,1 Jiasheng Tu11State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 2Chinese Pharmacopoeia Commission, Beijing, 3National Institute for Food and Drug Control, Beijing, People's Republic of ChinaAbstract: In order to limit the adverse reactions caused by polysorbate 80 in Taxotere®, a widely used formulation of docetaxel, a safe and effective nanocarrier for this drug has been developed based on micelles formed by a new class of well-defined polyoxyethylene sorbitol oleate (PSO with sorbitol as the matrix in aqueous solution. The physicochemical properties of the amphiphilic surfactant and the resulting micelles can be easily fine-tuned by the homogeneous sorbitol matrix and pure oleic acid. Composition, critical micelle concentration, and entrapment efficiency were investigated by ultraviolet visible spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, fluorospectrophotometry, and high-performance liquid chromatography. In vitro and in vivo evaluation revealed that PSO had exceptionally low hemolysis and histamine release rates compared with commercial polysorbate 80. Moreover, the tumor targeting delivery of PSO was investigated by in vivo imaging in S180 tumor-bearing mice. The results suggest that this novel delivery system, PSO, provides an acceptable alternative to polysorbate 80 for delivery of docetaxel. Further, due to the hypoallergenic nature of PSO, the mechanism of pseudoallergy caused by the polyoxyethylene nonionic surfactant was investigated. Based on in vitro cell analysis, it was assumed that the initial contact of polyoxyethylene nonionic surfactant with mast cells provoked pseudoallergy via polyamine receptor-mediated endocytosis.Keywords: polyoxyethylene nonionic surfactant, sorbitol, isosorbide, pseudoallergy

  1. Study to determine the improvement in neuropsychiatric symptoms after changing the responsible antiretroviral drug to nevirapine: the RELAX study

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    E Pedrol

    2012-11-01

    Full Text Available Objectives: Primary - evaluate the improvement in psychiatric symptoms attributable to changing the antiretroviral drug responsible for such symptoms to nevirapine (NVP. The tools used were a sleep test (the Pittsburgh Sleep Quality Index [PSQI] and the Hospital Anxiety and Depression Scale (HADS. Secondary - determine the neuropsychiatric disorders and evaluate adherence to treatment and quality of life. Methods: Prospective, observational post-authorisation study that included HIV-1 patients from 36 Spanish hospitals who satisfied the following criteria: age over 18 years; change of antiretroviral treatment to NVP due to CNS side-effects; a PSQI score >5 (significant sleep disturbance; a HADS score ≥10 on the day of starting NVP treatment; and no psychoactive drug treatment initiated during the 6 weeks prior to starting treatment with NVP. Other data gathered from the patients included clinical and demographic details and administration of the Epworth somnolence scale, the Medical Outcomes Study-short form 30 items (MOS-SF-30 quality of life scale and the Simplified Medication Adherence Questionnaire (SMAQ. Evaluations were performed at baseline, 1 and 3 months after the change. Results: 129 patients were included (73.6% men; mean age, 43.2 ± 9.8 years; 36.5% homosexual, 30.2% heterosexual; 28.7% drug users; 38% AIDS; 33.3% co-infection. The drug changed was efavirenz in 89.9% of cases. The reason for the change was sleep disturbances in 75.2%, anxiety in 65.1%, other psychiatric disturbances in 38.7%, attention disturbances in 31%, and other reasons in 31%; a mean of 2.4 neuropsychiatric disturbances were detected in each patient. CD4 rose from 582 ± 261 to 619 ± 299 (non-significant difference. Only three patients had developed an HIV viral load at the end of the study. The differences produced by the change are shown in Table 1. 29 patients withdrew from the study, for the following reasons: 9 for NVP-related toxicity (7 cases of rash

  2. Mapping of the WHO-ART terminology on Snomed CT to improve grouping of related adverse drug reactions.

    Science.gov (United States)

    Alecu, Iulian; Bousquet, Cedric; Mougin, Fleur; Jaulent, Marie-Christine

    2006-01-01

    The WHO-ART and MedDRA terminologies used for coding adverse drug reactions (ADR) do not provide formal definitions of terms. In order to improve groupings, we propose to map ADR terms to equivalent Snomed CT concepts through UMLS Metathesaurus. We performed such mappings on WHO-ART terms and can automatically classify them using a description logic definition expressing their synonymies. Our gold standard was a set of 13 MedDRA special search categories restricted to ADR terms available in WHO-ART. The overlapping of the groupings within the new structure of WHO-ART on the manually built MedDRA search categories showed a 71% success rate. We plan to improve our method in order to retrieve associative relations between WHO-ART terms.

  3. Self-microemulsifying drug-delivery system for improved oral bioavailability of pranlukast hemihydrate: preparation and evaluation.

    Science.gov (United States)

    Baek, Myoung-Ki; Lee, Jong-Hwa; Cho, Young-Ho; Kim, Hak-Hyung; Lee, Gye-Won

    2013-01-01

    The purpose of the present investigation was to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) for improving the oral absorption of a pranlukast hemihydrate (PLH), a very poorly water-soluble drug. An efficient self-microemulsifying vehicle for PLH was selected and optimized using solubility testing and phase diagram construction. The formulations were characterized by assessing self-emulsification performance, droplet size analysis, in vitro drug release characteristics and formulation stability studies. Optimized formulations for in vitro dissolution and bioavailability assessment were Triethylcitrate (TEC; 10%), Tween 20 (50%), Span 20 (25%), triethanolamine (5%), and benzyl alcohol (10%). The SMEDDS readily released the lipid phase to form a fine oil-in-water microemulsion with a narrow distribution size. Saturated solubilities of PLH from SMEDDS in water, pH 4.0 and 6.8, were over 150 times greater than that of plain PLH. The release of 100% PLH from SMEDDS was considerably greater compared to only 1.12% in simulated intestinal fluid (pH 6.8) from plain PLH after 2 hours. The PLH suspension with 0.5% sodium carboxymethylcellulose or 3% PLH-loaded SMEDDS was administrated at a dose of 40 mg/kg as PLH to fasted rats. The absorption of PLH from SMEDDS resulted in about a threefold increase in bioavailability compared with plain PLH aqueous suspension. Our studies illustrated that the potential use of the new SMEDDS can be used as a possible alternative to oral delivery of a poorly water-soluble drug such as PLH.

  4. Vendor-to-vendor education to improve malaria treatment by private drug outlets in Bungoma District, Kenya

    Directory of Open Access Journals (Sweden)

    Makama Sammy

    2003-05-01

    Full Text Available Abstract Background Private outlets are the main suppliers of uncomplicated malaria treatment in Africa. However, they are so numerous that they are difficult for governments to influence and regulate. This study's objective was to evaluate a low-cost outreach education (vendor-to-vendor programme to improve the private sector's compliance with malaria guidelines in Bungoma district, Kenya. The cornerstone of the programme was the district's training of 73 wholesalers who were equipped with customized job aids for distribution to small retailers. Methods Six months after training the wholesalers, the programme was evaluated using mystery shoppers. The shoppers posed as caretakers of sick children needing medication at 252 drug outlets. Afterwards, supervisors assessed the outlets' knowledge, drug stocks, and prices. Results The intervention seems to have had a significant impact on stocking patterns, malaria knowledge and prescribing practices of shops/kiosks, but not consistently on other types of outlets. About 32% of shops receiving job aids prescribed to mystery shoppers the approved first-line drug, sulfadoxine-pyremethamine, as compared to only 3% of the control shops. In the first six months, it is estimated that 500 outlets were reached, at a cost of about $8000. Conclusions Changing private sector knowledge and practices is widely acknowledged to be slow and difficult. The vendor-to-vendor programme seems a feasible district-level strategy for achieving significant improvements in knowledge and practices of shops/kiosks. However, alternate strategies will be needed to influence pharmacies and clinics. Overall, the impact will be only moderate unless national policies and programmes are also introduced.

  5. Hot melt extruded amorphous solid dispersion of posaconazole with improved bioavailability: investigating drug-polymer miscibility with advanced characterisation.

    Science.gov (United States)

    Fule, Ritesh; Amin, Purnima

    2014-01-01

    Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0-72) and C(max) of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0-72) and C(max) higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  6. Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

    Directory of Open Access Journals (Sweden)

    Ritesh Fule

    2014-01-01

    Full Text Available Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD with immediate release and improved bioavailability was prepared using Soluplus (Sol as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72 and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72 and Cmax higher than those with the commercial capsule (Noxafil. Molecular dynamic (MD simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  7. Optimizing the HRP-2 In Vitro Malaria Drug Susceptibility Assay Using a Reference Clone to Improve Comparisons of Plasmodium falciparum Field Isolates

    Science.gov (United States)

    2012-09-13

    available soon. Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum...Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum field isolates 5a...Date: 13 September 2012 14. ABSTRACT Apparent emerging artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia requires development

  8. Molecular Farming in Artemisia annua, a sustainable approach to improve anti-malarial drug production

    Directory of Open Access Journals (Sweden)

    Giuseppe ePulice

    2016-03-01

    Full Text Available Malaria is a parasite infection affecting millions of people worldwide. Even though progresses in prevention and treatment have been developed, 198 million cases of malaria occurred in 2013, resulting in 584000 estimated deaths. 90% of all malaria deaths occurred in Africa, mostly among children under the age of five. This article aims to review malaria’s history, epidemiology and current treatments, with a particular focus on the potential of molecular farming that use metabolic engineering in plants as effective anti-malarial solution. Malaria indeed represents an example of how a health problem on one hand, may eventually influence the proper development of a country due to the burden of the disease, and on the other hand, constitutes an opportunity for lucrative business of diverse stakeholders. In contrast, plant biofarming is here proposed as a sustainable alternative for the production not only of natural herbal repellents used for malaria prevention but also for the production of sustainable anti-malarial drugs like artemisinin used for primary parasite infection treatments.Artemisinin, a sesquiterpene lactone, is a natural anti-malarial compound that can be found in Artemisia annua plant. However, the low concentration of artemisinin in plant makes this molecule relatively expensive and difficult to meet the worldwide demand of Artemisinin Combination Therapies, especially for economically disadvantaged people in developing countries. The biosynthetic pathway of artemisinin, a process that only takes place in glandular secretory trichomes of A. annua, is relatively well elucidated, and significant efforts using plant genetic engineering have been made to increase the production of this compound. These include studies on diverse transcription factors, which all have been shown to regulate artemisinin genetic pathway and other biological processes. Therefore, genetic manipulation of these genes may be used as a cost-effective potential

  9. Lessons from history of socioeconomic improvements: a new approach to treating multi-drug-resistant tuberculosis.

    Science.gov (United States)

    Holloway, K L; Staub, K; Rühli, F; Henneberg, M

    2014-09-01

    This study investigated the trends in tuberculosis mortality through time in Switzerland. Information on the decline in mortality before chemotherapies were introduced may be useful in developing countries where drug-resistant tuberculosis is now becoming a major problem. Swiss data were collected from historical records and comparative data were obtained from the literature for England and Wales, New York, Japan, Brazil and Sierra Leone. Logistic curves were fitted to examine the rate of decline before introduction of pharmacotherapies and these show that the decline would have continued without the introduction of chemical therapies, including antibiotics. In Switzerland, England and Wales and New York, the decline had occurred long before the introduction of specific anti-tuberculosis agents. In Brazil and Japan, chemical therapy was co-incident with the decline in tuberculosis mortality rates. Overall, it is suggested that the effective control of tuberculosis can be achieved through a combination of chemical interventions, conservative therapy (rest, good nutrition, ventilation, etc.) as well as public health interventions addressing hygiene, nutrition, reducing exposure to infections and educating the population about tuberculosis.

  10. Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT).

    Science.gov (United States)

    Levy, Mark L; Dekhuijzen, P N R; Barnes, P J; Broeders, M; Corrigan, C J; Chawes, B L; Corbetta, L; Dubus, J C; Hausen, Th; Lavorini, F; Roche, N; Sanchis, J; Usmani, Omar S; Viejo, J; Vincken, W; Voshaar, Th; Crompton, G K; Pedersen, Soren

    2016-04-21

    Health professionals tasked with advising patients with asthma and chronic obstructive pulmonary disease (COPD) how to use inhaler devices properly and what to do about unwanted effects will be aware of a variety of commonly held precepts. The evidence for many of these is, however, lacking or old and therefore in need of re-examination. Few would disagree that facilitating and encouraging regular and proper use of inhaler devices for the treatment of asthma and COPD is critical for successful outcomes. It seems logical that the abandonment of unnecessary or ill-founded practices forms an integral part of this process: the use of inhalers is bewildering enough, particularly with regular introduction of new drugs, devices and ancillary equipment, without unnecessary and pointless adages. We review the evidence, or lack thereof, underlying ten items of inhaler 'lore' commonly passed on by health professionals to each other and thence to patients. The exercise is intended as a pragmatic, evidence-informed review by a group of clinicians with appropriate experience. It is not intended to be an exhaustive review of the literature; rather, we aim to stimulate debate, and to encourage researchers to challenge some of these ideas and to provide new, updated evidence on which to base relevant, meaningful advice in the future. The discussion on each item is followed by a formal, expert opinion by members of the ADMIT Working Group.

  11. In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy.

    Science.gov (United States)

    Kianmehr, Anvarsadat; Mohammadi, Hamid Shahbaz; Shokrgozar, Mohammad Ali; Omidinia, Eskandar

    2015-01-01

    The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. The EPO protein sequence was retrieved from NCBI protein sequence database. Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 3D structural modeling showed that attached carbohydrates were on the proper spatial position. The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug.

  12. Mixed PEG-PE/Vitamin E Tumor-Targeted Immunomicelles as Carriers for Poorly Soluble Anti-Cancer Drugs: Improved Drug Solubilization and Enhanced In Vitro Cytotoxicity

    Science.gov (United States)

    Sawant, Rupa R.; Sawant, Rishikesh M.; Torchilin, Vladimir P.

    2008-01-01

    Two poorly soluble, potent anticancer drugs, paclitaxel and camptothecin, were successfully solubilized by mixed micelles of polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) and vitamin E. Drug containing micelles were additionally modified with anti-nucleosome monoclonal antibody 2C5 (mAb 2C5), which can specifically bring micelles to tumor cells in vitro. The optimized micelles had an average size of about 13-to-22 nm and the immuno-modification of micelles did not significantly change it. The solubilization of both drugs by the mixed micelles was more efficient than by micelles made of PEG-PE alone. Solubilization of camptothecin in micelles prevented also the hydrolysis of active lactone form of the drug to inactive carboxylate form. Drug loaded mixed micelles and mAb 2C5-immunomicelles demonstrated significantly higher in vitro cytotoxicity than free drug against various cancer cell lines. PMID:18583114

  13. Improvements in analytical methodology for the determination of frequently consumed illicit drugs in urban wastewater.

    Science.gov (United States)

    Bijlsma, Lubertus; Beltrán, Eduardo; Boix, Clara; Sancho, Juan V; Hernández, Félix

    2014-07-01

    Rapid and sensitive analytical methodology based on ultra high-performance liquid chromatography-tandem mass spectrometry has been developed for the determination of widely consumed drugs of abuse (amphetamines, MDMA, cocaine, opioids, cannabis and ketamine) and their major metabolites in urban wastewaters. Sample clean-up and pre-concentration was performed by a generic off-line SPE procedure using Oasis HLB. Special effort was made to incorporate amphetamine, which was found highly problematic in the wastewater samples tested, including an additional clean-up with Oasis MCX SPE and dispersive primary secondary amine. Correction for possible SPE losses or degradation during storage was made by the use of isotope-labelled internal standards (ILIS), available for all compounds, which were added to the samples as surrogates. Although ILIS were also efficient for matrix effects correction, the strong ionization suppression observed was not eliminated; therefore, a four-fold dilution prior to SPE was applied to influent wastewaters and a low injection volume was selected (3 μL), in order to reach a compromise between matrix effects, chromatographic performance and sensitivity. The method was validated at 25 and 200 ng L(-1) (effluent), and 100 and 800 ng L(-1) (influent), obtaining limits of quantification (i.e. the lowest level that the compound can be quantified and also confirmed with at least two MS/MS transitions) between 0.4-25 ng L(-1) (effluent) and 2-100 ng L(-1) (influent). The applicability of the method was demonstrated by analysis of 14 influent and 14 effluent wastewater samples collected over 2 weeks in Castellón (Spain) within a European collaborative study.

  14. Triazole derivatives with improved in vitro antifungal activity over azole drugs

    Directory of Open Access Journals (Sweden)

    Yu S

    2014-04-01

    Full Text Available Shichong Yu,1,* Xiaoyun Chai,1,* Yanwei Wang,1 Yongbing Cao,2 Jun Zhang,3 Qiuye Wu,1 Dazhi Zhang,1 Yuanying Jiang,2 Tianhua Yan,4 Qingyan Sun11Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 3Overseas Education Faculty of the Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: A series of triazole antifungal agents with piperidine side chains was designed and synthesized. The results of antifungal tests against eight human pathogenic fungi in vitro showed that all the compounds exhibited moderate-to-excellent activities. Molecular docking between 8d and the active site of Candida albicans CYP51 was provided based on the computational docking results. The triazole interacts with the iron of the heme group. The difluorophenyl group is located in the S3 subsite and its fluorine atom (2-F can form H-bonds with Gly307. The side chain is oriented into the S4 subsite and formed hydrophobic and van der Waals interactions with the amino residues. Moreover, the phenyl group in the side chain interacts with the phenol group of Phe380 through the formation of π–π face-to-edge interactions.Keywords: synthesis, CYP51, molecular docking, azole agents

  15. Adolescent athletes and the demand and supply of drugs to improve their performance.

    Science.gov (United States)

    Laure, Patrick; Binsinger, Caroline

    2005-09-01

    The aim of this study was to gather information into the principal methods and means employed to supply adolescents with doping agents and others substances used to improve their sporting performance. We conducted a nation wide study in France among adolescent athletes, using a self-completed questionnaire. Exploitable questionnaires (n = 6402) were returned, corresponding to 48.9% for the girls and 51.1% for the boys, both aged on average from 16.1 ± 2.2 years. These adolescents practise on average 10.0 ± 5.2 hours of sport per week. 21.9% participate on a national or international competition level. Of our respondents, 4.0% (95% confidence interval: 3.5% - 4.5%) say they have been enticed into using products which are prohibited for athletes. 10.3% of the adolescents say that they have received substances to improve their performance at least once from an average of two different people. It was mostly a friend, their parents and the family doctor. On average, in 33.2% of the cases, the adolescent received the product without asking for it, and in nearly half the cases (46.6%), the adolescent paid for the product. We feel that it is necessary to better understand the ways in which this black market functions: for example; the initial sources of the products sold, the number and the 'profiles' of the dealers, the general organisation of the market and the sums of money involved. Key PointsThis study confirms the existence of a 'black market' for products to improve performance, which is directed at adolescent athletes engaged in high-level competitions.This market is characterized by its ease of accessibility and also the diversity of its 'suppliers', the two main sources being friends and parents.

  16. Nanomedicine-nanoemulsion formulation improves safety and efficacy of the anti-cancer drug paclitaxel according to preclinical assessment.

    Science.gov (United States)

    Lee, King C; Maturo, Claudia; Rodriguez, Robert; Nguyen, Hoang-Lan; Shorr, Robert

    2011-08-01

    Paclitaxel is an important anticancer drug and is currently used to treat a variety of cancers, including ovarian carcinomas, breast cancer, non-small cell lung cancer, and AIDS-related Kaposi's sarcoma. The objectives of the studies were to assess and compare the safety and efficacy of EmPAC (a newly developed nanoemulsion formulation of paclitaxel) versus Taxol (the injectable formulation of paclitaxel involving the use of polyethylated or polyoxyl castor oil currently used in the clinic). The objectives were also to investigate the mechanism for the improved safety and efficacy of EmPAC over Taxol. These results showed that EmPAC had better anti-tumor efficacy than Taxol, according to in vitro cell culture studies and studies in animal tumor models. EmPAC had improved anti-tumor efficacy even in tumor cell lines that are known to be multi-drug resistant. Part of the mechanism of action for the improved efficacy may be related to EmPAC inducing greater cellular uptake of paclitaxel into tumor cells than Taxol did, according to the in vitro cell culture radioactive-labeled studies and in vitro cell culture antibody studies. It may also partly be because EmPAC delivered more paclitaxel to the tumor mass than Taxol, while the delivery of paclitaxel to other tissues (e.g., blood, muscle, liver, spleen, kidney and lung) were similar between the two formulations of paclitaxel, according to studies in animals with tumor xenograft. EmPAC also had better safety than Taxol according to toxicology studies in rabbits. This may be because EmPAC does not contain the toxic ingredients used in formulating Taxol (such as polyethylated or polyoxyl castor oil). These results support the clinical development of the nanoemulsion formulation of paclitaxel.

  17. Adolescent Athletes and the Demand and Supply of Drugs to Improve Their Performance

    OpenAIRE

    Patrick Laure; Caroline Binsinger

    2005-01-01

    The aim of this study was to gather information into the principal methods and means employed to supply adolescents with doping agents and others substances used to improve their sporting performance. We conducted a nation wide study in France among adolescent athletes, using a self-completed questionnaire. Exploitable questionnaires (n = 6402) were returned, corresponding to 48.9% for the girls and 51.1% for the boys, both aged on average from 16.1 ± 2.2 years. These adolescents practise on ...

  18. ADOLESCENT ATHLETES AND THE DEMAND AND SUPPLY OF DRUGS TO IMPROVE THEIR PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Patrick Laure

    2005-09-01

    Full Text Available The aim of this study was to gather information into the principal methods and means employed to supply adolescents with doping agents and others substances used to improve their sporting performance. We conducted a nation wide study in France among adolescent athletes, using a self-completed questionnaire. Exploitable questionnaires (n = 6402 were returned, corresponding to 48.9% for the girls and 51.1% for the boys, both aged on average from 16.1 ± 2.2 years. These adolescents practise on average 10.0 ± 5.2 hours of sport per week. 21.9% participate on a national or international competition level. Of our respondents, 4.0% (95% confidence interval: 3.5% - 4.5% say they have been enticed into using products which are prohibited for athletes. 10.3% of the adolescents say that they have received substances to improve their performance at least once from an average of two different people. It was mostly a friend, their parents and the family doctor. On average, in 33.2% of the cases, the adolescent received the product without asking for it, and in nearly half the cases (46.6%, the adolescent paid for the product. We feel that it is necessary to better understand the ways in which this black market functions: for example; the initial sources of the products sold, the number and the 'profiles' of the dealers, the general organisation of the market and the sums of money involved

  19. Implementation and evaluation of a multisite drug usage evaluation program across Australian hospitals - a quality improvement initiative

    Directory of Open Access Journals (Sweden)

    Robertson Marion B

    2011-08-01

    Full Text Available Abstract Background With the use of medicines being a broad and extensive part of health management, mechanisms to ensure quality use of medicines are essential. Drug usage evaluation (DUE is an evidence-based quality improvement methodology, designed to improve the quality, safety and cost-effectiveness of drug use. The purpose of this paper is to describe a national DUE methodology used to improve health care delivery across the continuum through multi-faceted intervention involving audit and feedback, academic detailing and system change, and a qualitative assessment of the methodology, as illustrated by the Acute Postoperative Pain Management (APOP project. Methods An established methodology, consisting of a baseline audit of inpatient medical records, structured patient interviews and general practitioner surveys, followed by an educational intervention and follow-up audit, is used. Australian hospitals, including private, public, metropolitan and regional, are invited to participate on a voluntary basis. De-identified data collected by hospitals are collated and evaluated nationally to provide descriptive comparative analyses. Hospitals benchmark their practices against state and national results to facilitate change. The educational intervention consists of academic detailing, group education, audit and feedback, point-of-prescribing prompts and system changes. A repeat data collection is undertaken to assess changes in practice. An online qualitative survey was undertaken to evaluate the APOP program. Qualitative assessment of hospitals' perceptions of the effectiveness of the overall DUE methodology and changes in procedure/prescribing/policy/clinical practice which resulted from participation were elicited. Results 62 hospitals participated in the APOP project. Among 23 respondents to the evaluation survey, 18 (78% reported improvements in the documentation of pain scores at their hospital. 15 (65% strongly agreed or agreed that

  20. Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

    Science.gov (United States)

    Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

    2015-11-01

    Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

  1. Gemals, a new drug candidate, extends lifespan and improves electromyographic parameters in a rat model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Nicaise, Charles; Coupier, Jerome; Dabadie, Marie-Pierre; De Decker, Robert; Mangas, Arturo; Bodet, Dominique; Poncelet, Luc; Geffard, Michel; Pochet, Roland

    2008-04-01

    Amyotrophic lateral sclerosis (ALS) is a fatal disease involving selective and progressive degeneration and death of motor neurons. ALS is a multifactorial disease in which oxidative stress, glutamate excitotoxicity, intracellular aggregates, neurofilamentous disorganization, zinc excitotoxicity, mitochondrial damage, neuroinflammation, abnormalities in growth factors and apoptosis play a role. Any therapeutic approach to delay or stop the evolution of ALS should therefore ideally target these multiple pathways leading to motor neuron death. We have developed a combination therapy (Gemals) composed of functional polypeptides (fatty acids, free radical scavengers and amino acids linked to poly-L-lysine), chosen according to their known potentiality for regeneration or protection of neuronal components such as myelin, axon transport and mitochondria. We found that Gemals significantly extended lifespan and improved electromyographic parameters in a SOD1(G93A) rat model. The use of two drug concentrations indicated a possible dose dependence. These initial findings open the way to further investigation necessary to validate this new drug as a candidate for ALS treatment.

  2. Investigating the Use of Polymeric Binders in Twin Screw Melt Granulation Process for Improving Compactibility of Drugs.

    Science.gov (United States)

    Batra, Amol; Desai, Dipen; Serajuddin, Abu T M

    2017-01-01

    Traditionally, the melt granulation for pharmaceutical products was performed at low temperature (twin screw extruder where the processing temperature could be increased to as high as 180°C and polymers with high Tg could be used as binders. In this study, different polymeric binders were screened for their suitability in improving compactibility of 2 drugs, metformin hydrochloride and acetaminophen, by twin screw melt granulation. Processing temperatures for the 2 drugs were set at 180°C and 130°C, respectively. Screw configuration, screw speed, and feed rate were optimized such that all polymeric binders used produced granules. Several hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and methacrylate-based polymers, including Klucel(®) EXF, Eudragit(®) EPO, and Soluplus(®), demonstrated good tablet tensile strength (>2 MPa) when granules were produced using only 10% wt/wt polymer concentration. Certain polymers provided acceptable compactibility even at 5% wt/wt. Thus, twin screw melt granulation process may be used with different polymers at a wide range of temperature. Due to low excipient concentration, this granulation method is especially suitable for high-dose tablets.

  3. Applying human factors to develop an improved package design for (Rx) medication drug labels in a pharmacy setting.

    Science.gov (United States)

    Gerhart, Julie M; Spriggs, Holly; Hampton, Tonja W; Hoy, Rose Mary B; Strochlic, Allison Y; Proulx, Susan; Goetchius, Debra B

    2015-12-01

    As many as 98,000 people die every year from preventable medical errors. Among pharmacists, the most common error reported is the selection of the wrong drug. Merck met with the U.S. Food and Drug Administration (FDA) to discuss the optimization of the U.S. label for solid oral dosage forms of Merck medications. These discussions led to the development of revised label designs for six products that were then evaluated using failure modes and effects analysis and an expert review by human factors specialists. There were no errors among 425 filled prescriptions in the validation test of the final label. Key changes to the original labels include the use of a non-branded logo, high-contrast color bands for dosage strength, and an enhanced three-dimensional tablet image. The redesigned labels were approved by the US FDA in June 2011. The redesigned label should improve the accurate selection of medications from pharmacy shelves. Copyright © 2015 Elsevier Ltd and National Safety Council. All rights reserved.

  4. Improved outcomes of elderly patients treated with drug-eluting versus bare metal stents in large coronary arteries

    DEFF Research Database (Denmark)

    Kurz, David J; Bernheim, Alain M; Tüller, David

    2015-01-01

    BACKGROUND: Drug-eluting stents (DES) improve outcomes in elderly patients with small coronary artery disease compared with bare-metal stents (BMS), but randomized data in elderly patients in need of large coronary stents are not available. METHODS: Planned secondary analysis of patients ≥75 years...... recruited to the "BASKET-PROVE" trial, in which 2,314 patients undergoing percutaneous coronary intervention for large (≥3.0 mm) native vessel disease were randomized 2:1 to DES (everolimus- vs sirolimus-eluting stents 1:1) versus BMS. All patients received 12 months of dual antiplatelet therapy....... The primary end point was a composite of cardiac death or nonfatal myocardial infarction at 2 years. RESULTS: Comparison of DES versus BMS among 405 patients ≥75 years showed significantly lower rates of the primary end point for DES (5.0% vs 11.6%; hazard ration (HR) 0.64 [0.44-0.91]; P = .014). Rates...

  5. A Newly Improved Modified Method Development and Validation of Bromofenac Sodium Sesquihydrate in Bulk Drug Manufacturing

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Yelamanchi V

    2016-10-01

    Full Text Available The main objective of this study was to develop a simple, efficient, specific, precise and accurate newly improved modified Reverse Phase High Performance Liquid Chromatographic Purity (or Related substance method for bromofenac sodium sesquihydrate active pharmaceuticals ingredient dosage form. Validation of analytical method is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled as per ICH, USP, BP or any other suitable regulatory guidelines. The Reverse Phase High Performance Liquid Chromatographic Gradient method was developed by utilizing Waters Symmetry C8, 150x4.6mm, 3.5µm on Waters 2487 series Liquid Chromatograph. The retention time of bromofenac sodium sesquihydrate was found to be 5.973minutes. Considering all the results of validation parameters simplicity of the method and the cost effectiveness of the overall procedure, it is possible to conclude that the developed method can be suitable for the regular quality control determination of bromofenac sodium sesquihydrate in bulk as well as pharmaceutical dosage form.The developed Reverse Phase High Performance Liquid Chromatographic Purity (or Related substance method for bromofenac sodium sesquihydrate active pharmaceuticals ingredient method was validated with respect to System Suitability , linearity, , precision ,Range, Ruggedness, Test Solution and Mobile phase stability ,Robustness..

  6. Improved mucoadhesive properties of self-nanoemulsifying drug delivery systems (SNEDDS) by introducing acyl chitosan.

    Science.gov (United States)

    Efiana, Nuri Ari; Mahmood, Arshad; Lam, Hung Thanh; Zupančič, Ožbej; Leonaviciute, Gintare; Bernkop-Schnürch, Andreas

    2017-03-15

    This study was aimed to improve the mucoadhesive properties of SNEDDS by the incorporation of acyl chitosan including octanoyl chitosan (OC), lauroyl chitosan (LC) and palmitoyl chitosan (PC). SNEDDS and acyl chitosan SNEDDS were characterized regarding droplet size and zeta potential. Their mucoadhesivity on porcine intestinal mucosa was evaluated by falling liquid film technique using Sudan Red G as marker. Degree of substitution of chitosan was determined to be 52.8%, 64.8 and 48.5% for OC, LC and PC, respectively. SNEDDS and acyl chitosan SNEDDS displayed a droplet size less than 50nm and 80-300nm as well as a zeta potential of -0.2 to -1.6 and 0.05 to 0.99mV, respectively. Introducing 2% acyl chitosan into SNEDDS increased the residence time of SNEDDS on intestinal mucosa 2-fold. It is concluded that due to the incorporation of acyl chitosan into SNEDDS, their mucoadhesive properties can be increased. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Criticisms of drugs in early development for the treatment of depression: what can be improved?

    Science.gov (United States)

    Wang, Sheng-Min; Han, Changsu; Pae, Chi-Un

    2015-04-01

    Major depressive disorder (MDD) is a common and debilitating mental illness, which leads to serious functional impairment in patients, and treatment-wise, there are currently a number of different classes of antidepressants already on the market. However, emerging evidence from numerous clinical trials has confirmed that there is still an unmet need for antidepressant efficacy in terms of response and remission. Approximately only 30% of patients with MDD may remit after adequate treatment with antidepressants in clinical practice. The drawbacks of the currently available antidepressants also include inadequate overall efficacy, safety issues and the lag prior to onset of clinical improvement. The need for new agents with novel mechanisms of action has led to the development of several newer antidepressants including vilazodone, edivoxetine, ketamine, atomoxetine and vortioxetine, which have been approved for the treatment of MDD. However, the efficacy and safety of these next-generation antidepressants, in clinical trials, are still unsatisfactory. This paper provides a brief updated overview of the progress and critical limitations in the development of novel antidepressants.

  8. Evaluation of Three Amorphous Drug Delivery Technologies to Improve the Oral Absorption of Flubendazole.

    Science.gov (United States)

    Vialpando, Monica; Smulders, Stefanie; Bone, Scott; Jager, Casey; Vodak, David; Van Speybroeck, Michiel; Verheyen, Loes; Backx, Katrien; Boeykens, Peter; Brewster, Marcus E; Ceulemans, Jens; Novoa de Armas, Hector; Van Geel, Katrien; Kesselaers, Emma; Hillewaert, Vera; Lachau-Durand, Sophie; Meurs, Greet; Psathas, Petros; Van Hove, Ben; Verreck, Geert; Voets, Marieke; Weuts, Ilse; Mackie, Claire

    2016-09-01

    This study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH. All formulations remained amorphous at 25°C/60% RH. Only the MPSDD formulation containing HPMCAS-M and 3/7 (wt./wt.) FLU/OMS did not crystallize following 40°C/75% RH exposure. The OMS and MPSDD formulations contained the lowest and highest amount of hydrolyzed degradant, respectively. All formulations were dosed to rats at 20 mg/kg in suspension. One FLU/OMS formulation was also dosed as a capsule blend. Plasma concentration profiles were determined following a single dose. In vivo findings show that the OMS capsule and suspension resulted in the overall highest area under the curve and Cmax values, respectively. These results cross-evaluate various amorphous formulations and provide a link to enhanced biopharmaceutical performance.

  9. Opioid receptor activation triggering downregulation of cAMP improves effectiveness of anti-cancer drugs in treatment of glioblastoma

    Science.gov (United States)

    Friesen, Claudia; Hormann, Inis; Roscher, Mareike; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf; Debatin, Klaus-Michael; Miltner, Erich

    2014-01-01

    Glioblastoma are the most frequent and malignant human brain tumors, having a very poor prognosis. The enhanced radio- and chemoresistance of glioblastoma and the glioblastoma stem cells might be the main reason why conventional therapies fail. The second messenger cyclic AMP (cAMP) controls cell proliferation, differentiation, and apoptosis. Downregulation of cAMP sensitizes tumor cells for anti-cancer treatment. Opioid receptor agonists triggering opioid receptors can activate inhibitory Gi proteins, which, in turn, block adenylyl cyclase activity reducing cAMP. In this study, we show that downregulation of cAMP by opioid receptor activation improves the effectiveness of anti-cancer drugs in treatment of glioblastoma. The µ-opioid receptor agonist D,L-methadone sensitizes glioblastoma as well as the untreatable glioblastoma stem cells for doxorubicin-induced apoptosis and activation of apoptosis pathways by reversing deficient caspase activation and deficient downregulation of XIAP and Bcl-xL, playing critical roles in glioblastomas’ resistance. Blocking opioid receptors using the opioid receptor antagonist naloxone or increasing intracellular cAMP by 3-isobutyl-1-methylxanthine (IBMX) strongly reduced opioid receptor agonist-induced sensitization for doxorubicin. In addition, the opioid receptor agonist D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux, whereas doxorubicin increased opioid receptor expression in glioblastomas. Furthermore, opioid receptor activation using D,L-methadone inhibited tumor growth significantly in vivo. Our findings suggest that opioid receptor activation triggering downregulation of cAMP is a promising strategy to inhibit tumor growth and to improve the effectiveness of anti-cancer drugs in treatment of glioblastoma and in killing glioblastoma stem cells. PMID:24626197

  10. Self-microemulsifying drug-delivery system for improved oral bioavailability of pranlukast hemihydrate: preparation and evaluation

    Directory of Open Access Journals (Sweden)

    Baek MK

    2013-01-01

    Full Text Available Myoung-Ki Baek,1,* Jong-Hwa Lee,2,* Young-Ho Cho,3 Hak-Hyung Kim,4 Gye-Won Lee3 1Life Science R&D Park, SK Biopharmaceuticals Co, LTD, Daejeon, Republic of Korea; 2Toxicology Center, Korea Institute of Toxicology, Daejeon, Republic of Korea; 3Department of Pharmaceutical Engineering, Konyang University, Nonsan, Republic of Korea; 4R&D Center, Pharvis Korea Pharm, Ansan, Republic of Korea *These authors contributed equally to this workAbstract: The purpose of the present investigation was to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS for improving the oral absorption of a pranlukast hemihydrate (PLH, a very poorly water-soluble drug. An efficient self-microemulsifying vehicle for PLH was selected and optimized using solubility testing and phase diagram construction. The formulations were characterized by assessing self-emulsification performance, droplet size analysis, in vitro drug release characteristics and formulation stability studies. Optimized formulations for in vitro dissolution and bioavailability assessment were Triethylcitrate (TEC; 10%, Tween 20 (50%, Span 20 (25%, triethanolamine (5%, and benzyl alcohol (10%. The SMEDDS readily released the lipid phase to form a fine oil-in-water microemulsion with a narrow distribution size. Saturated solubilities of PLH from SMEDDS in water, pH 4.0 and 6.8, were over 150 times greater than that of plain PLH. The release of 100% PLH from SMEDDS was considerably greater compared to only 1.12% in simulated intestinal fluid (pH 6.8 from plain PLH after 2 hours. The PLH suspension with 0.5% sodium carboxymethylcellulose or 3% PLH-loaded SMEDDS was administrated at a dose of 40 mg/kg as PLH to fasted rats. The absorption of PLH from SMEDDS resulted in about a threefold increase in bioavailability compared with plain PLH aqueous suspension. Our studies illustrated that the potential use of the new SMEDDS can be used as a possible alternative to oral delivery of a poorly

  11. Technical Modification Within the Healthcare Industry: Improving Both the Efficacy of the National Drug Code Carrier and the Accessibility of Electronic Health Records to Reduce Adverse Drug Events

    Science.gov (United States)

    2013-06-01

    an ADE. A few scenarios from the perspective of a clinician at the doctor’s office, an EMT, and a pharmacist all tasked to administer drugs to a...has also been made. The final assumption is that the EMT, pharmacist , and clinician , all have the proper credentials and permissions to 93...Figure 39. Clinician drug interaction cross-check with an indirect-encoded/hybrid QR code In the case of an EMT or pharmacist , the procedures

  12. [Rising attention to the market to ratio meet demand of improving efficiency of pharmaceutical circulation--based on complicated variety and specification of drugs].

    Science.gov (United States)

    Chen, Zhaoxing; Sun, Lihua

    2010-05-01

    Analyzing the complicated variety and specification of drugs and the objective demand of pharmaceutical circulation, to seek out the key factors in improving the efficiency of pharmaceutical circulation, for putting forward suggestions to promote the development of pharmaceutical circulation in China. The conclusion is drawed from industrial organization theory and successful experience of foreign countries, high market attention met with the demand of complicated variety and specification of drugs in pharmaceutical circulation.

  13. Improving psychotropic drug prescription in nursing home patients with dementia : design of a cluster randomized controlled trial

    NARCIS (Netherlands)

    Smeets, Claudia H. W.; Smalbrugge, Martin; Gerritsen, Debby L.; Nelissen-Vrancken, Marjorie H. J. M. G.; Wetzels, Roland B.; van der Spek, Klaas; Zuidema, Sytse U.; Koopmans, Raymond T. C. M.

    2013-01-01

    Background: Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are

  14. Improved Completion Rates and Characterization of Drug Reactions with an Intensive Chagas Disease Treatment Program in Rural Bolivia

    Science.gov (United States)

    Tornheim, Jeffrey A.; Lozano Beltran, Daniel F.; Gilman, Robert H.; Castellon, Mario; Solano Mercado, Marco A.; Sullca, Walter; Torrico, Faustino; Bern, Caryn

    2013-01-01

    Background Chagas disease treatment is limited by drug availability, adverse side effect profiles of available medications, and poor adherence. Methods Adult Chagas disease patients initiating 60-days of benznidazole were randomized to weekly or twice-weekly evaluations of medication adherence and screening for adverse drug events (ADEs). Mid-week evaluations employed phone-based evaluations. Adherence was measured by self-report, pill counts with intentional over-distribution, and Medication Event Monitoring Systems (MEMS). Prospective data were compared to historical controls treated with benznidazole at the same hospital. Results 162 prospective patients were compared to 172 historical patients. Pill counts correlated well with MEMS data (R = 0.498 for 7-day intervals, R = 0.872 for intervals >7 days). Treatment completion rates were higher among prospective than historical patients (82.1% vs. 65.1%), primarily due to lower abandonment rates. Rates of ADEs were lower among prospective than historical patients (56.8% vs. 66.9%). Twice-weekly evaluations increased identification of mild ADEs, prompting higher suspension rates than weekly evaluations. While twice-weekly evaluations identified ADEs earlier, they did not reduce incidence of moderate or severe ADEs. Many dermatologic ADEs were moderately severe upon presentation (35.6%), were not reduced by use of antihistamines, occurred among adult patients of all ages, and occurred throughout treatment, rather than the first few weeks alone. Conclusions Intensive management improved completion and identified more ADEs, but did not reduce moderate or severe ADEs. Risk of dermatologic ADEs cannot be reduced by selecting younger adults or monitoring only during the first few weeks of treatment. Pill counts and phone-based encounters are reliable tools for treatment programming in rural Bolivia. PMID:24069472

  15. Submicron-bubble-enhanced focused ultrasound for blood-brain barrier disruption and improved CNS drug delivery.

    Directory of Open Access Journals (Sweden)

    Ching-Hsiang Fan

    Full Text Available The use of focused ultrasound (FUS with microbubbles has been proven to induce transient blood-brain barrier opening (BBB-opening. However, FUS-induced inertial cavitation of microbubbles can also result in erythrocyte extravasations. Here we investigated whether induction of submicron bubbles to oscillate at their resonant frequency would reduce inertial cavitation during BBB-opening and thereby eliminate erythrocyte extravasations in a rat brain model. FUS was delivered with acoustic pressures of 0.1-4.5 MPa using either in-house manufactured submicron bubbles or standard SonoVue microbubbles. Wideband and subharmonic emissions from bubbles were used to quantify inertial and stable cavitation, respectively. Erythrocyte extravasations were evaluated by in vivo post-treatment magnetic resonance susceptibility-weighted imaging, and finally by histological confirmation. We found that excitation of submicron bubbles with resonant frequency-matched FUS (10 MHz can greatly limit inertial cavitation while enhancing stable cavitation. The BBB-opening was mainly caused by stable cavitation, whereas the erythrocyte extravasation was closely correlated with inertial cavitation. Our technique allows extensive reduction of inertial cavitation to induce safe BBB-opening. Furthermore, the safety issue of BBB-opening was not compromised by prolonging FUS exposure time, and the local drug concentrations in the brain tissues were significantly improved to 60 times (BCNU; 18.6 µg versus 0.3 µg by using chemotherapeutic agent-loaded submicron bubbles with FUS. This study provides important information towards the goal of successfully translating FUS brain drug delivery into clinical use.

  16. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2014-01-15

    Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance.

  17. [HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

    Science.gov (United States)

    Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

    2017-04-01

    In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands

  18. Up-Conversion Y2O3:Yb(3+),Er(3+) Hollow Spherical Drug Carrier with Improved Degradability for Cancer Treatment.

    Science.gov (United States)

    Ge, Kun; Zhang, Cuimiao; Sun, Wentong; Liu, Huifang; Jin, Yi; Li, Zhenhua; Liang, Xing-Jie; Jia, Guang; Zhang, Jinchao

    2016-09-28

    The rare earth hollow spheres with up-conversion luminescence properties have shown potential applications in drug delivery and bioimaging fields. However, there have been few reports for the degradation properties of rare earth oxide drug carriers. Herein, uniform and well-dispersed Y2O3:Yb(3+),Er(3+) hollow spheres (YOHSs) have been fabricated by a general Pechini sol-gel process with melamine formaldehyde colloidal spheres as template. The novel YOHSs with up-conversion luminescence has good drug loading amount and drug-release efficiency; moreover, it exhibits pH-responsive release patterns. In particular, the YOHSs sample exhibits low cytotoxicity and excellent degradable properties in acid buffer. After the sample was loaded with anticancer drug doxorubicin (DOX), the antitumor result in vitro indicates that YOHS-DOX might be effective in cancer treatment. The animal imaging test also reveals that the YOHSs drug carrier can be used as an outstanding luminescent probe for bioimaging in vivo application prospects. The results suggest that the degradable drug carrier with up-conversion luminescence may enhance the delivery efficiency of drugs and improve the cancer therapy in clinical applications.

  19. Improving Drug Administration to Reduce Drug Use Error Rare of Pharmacy Intravenous Admixture Service%完善药品管理降低静脉用药调配中心药品使用差错率

    Institute of Scientific and Technical Information of China (English)

    周璐; 陈海燕

    2015-01-01

    Objective To reduce drug using error rare of pharmacy intravenous admixture service (PIVAS) by improving drug administration. Methods Drug using errors in PIVAS from March 2014 to August in 2014 were analyzed retrospective-ly, and during this time some measures about drug administration were taken. Results Drug using errors were decreased from 162 cases in March to 39 cases in August in 2014,and the drug using error rate was reduced from 2.04‰to 0.48‰(P<0.05). Conclusion Drug administration played a vital operation in PIVAS, and improving drug management can not only reduce the error rate in PIVAS but also reduce medical risks.%目的 完善药品管理,降低儿童医院静脉用药调配中心(PIVAS)药品使用差错率.方法 回顾该院PIVAS2014年3月-2014年8月,分析完善药品管理前后,药品使用差错的变化情况. 结果 药品使用差错由2014年3月的162例减少为8月的39例,药品使用差错率由2.04‰降为0.48‰(P<0.05). 结论 药品管理在PIVAS运行中起着至关重要的作用,做好药品管理,可降低PIVAS差错率,减少医疗隐患.

  20. Improving Drug Design: An Update on Recent Applications of Efficiency Metrics, Strategies for Replacing Problematic Elements, and Compounds in Nontraditional Drug Space.

    Science.gov (United States)

    Meanwell, Nicholas A

    2016-04-18

    Drug discovery and development is a complex and lengthy enterprise that suffers from high rates of candidate attrition at all stages of the process. The physical, biological, and toxicological properties of a drug candidate are inextricably linked to its structure, and once a molecule has been synthesized, all subsequent studies along the development path are focused only on assessing and understanding its properties in greater detail. Unfortunately, a full prediction of the biological properties of a molecule from an analysis of its 2- or 3-dimensional structure is currently beyond our expertise. This backdrop mandates that considerable care be taken at the design stage if a molecule is to be successful in testing a mechanistic concept underlying a disease process and to progress into late stage clinical trials and, ultimately, marketing approval. While there are multiple potential causes of candidate attrition, an introspective analysis of drug design practices over the past decade has focused attention on the perception that contemporary molecules are unnecessarily obese, burdened by high molecular weight and excessive lipophilicity. This practice is believed to have its roots in the singular pursuit of enhancing potency during lead optimization rather than adopting a more holistic approach to drug design that gives broader consideration to how structural features affect developability properties. In an effort to provide the medicinal chemistry community with practical guideposts to enhancing compound quality in the drug design phase and which can readily be applied, a series of efficiency indices have been proposed that attempt to define aspects of compound quality in the context of a series of physicochemical parameters. Of these metrics, lipophilic ligand efficiency (LLE or LipE), which provides an index of the dependence of the potency of a molecule on its intrinsic lipophilicity, has been characterized as the most robust metric that has potential for broad

  1. Curcumin-coordinated nanoparticles with improved stability for reactive oxygen species-responsive drug delivery in lung cancer therapy

    Directory of Open Access Journals (Sweden)

    Luo CQ

    2017-01-01

    Full Text Available Cheng-Qiong Luo,1–3,* Lei Xing,1–3,* Peng-Fei Cui,1 Jian-Bin Qiao,1 Yu-Jing He,1 Bao-An Chen,4 Liang Jin,1,2,5 Hu-Lin Jiang1–3 1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, 2Jiangsu Key Laboratory of Drug Screening, 3Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, 4Department of Hematology, The Affiliated Zhongda Hospital of Southeast University, 5School of Life Science and Technology, China Pharmaceutical University, Nanjing, China *These authors contributed equally to this work Background: The natural compound curcumin (Cur can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS-responsive nanoparticle using the interaction between boronic acid and Cur. Materials and methods: We synthesized a highly biocompatible 4-(hydroxymethyl phenylboronic acid (HPBA-modified poly(ethylene glycol (PEG-grafted poly(acrylic acid polymer (PPH and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC based on the interaction between boronic acid and Cur. The mean diameter of the Cur-coordinated PPHC nanoparticle was 163.8 nm and its zeta potential was –0.31 mV. The Cur-coordinated PPHC nanoparticle improved Cur stability in physiological environment and could timely release Cur in response to hydrogen peroxide (H2O2. PPHC nanoparticles demonstrated potent antiproliferative effect in vitro in A549 cancer cells. Furthermore, the viability of cells treated with PPHC nanoparticles was significantly increased in the presence of N-acetyl-cysteine (NAC, which blocks Cur release through ROS inhibition. Simultaneously, the ROS level measured in A549 cells after incubation with PPHC nanoparticles exhibited an obvious downregulation, which further proved that ROS

  2. Improving Coverage and Compliance in Mass Drug Administration for the Elimination of LF in Two 'Endgame' Districts in Indonesia Using Micronarrative Surveys.

    Science.gov (United States)

    Krentel, Alison; Damayanti, Rita; Titaley, Christiana Rialine; Suharno, Nugroho; Bradley, Mark; Lynam, Timothy

    2016-11-01

    As the Global Programme to Eliminate Lymphatic Filariasis (LF) approaches its 2020 goal, an increasing number of districts will enter the endgame phase where drug coverage rates from mass drug administration (MDA) are used to assess whether MDA can be stopped. As reported, the gap between reported and actual drug coverage in some contexts has overestimated the true rates, thus causing premature administration of transmission assessment surveys (TAS) that detect ongoing LF transmission. In these cases, districts must continue with additional rounds of MDA. Two districts in Indonesia (Agam District, Depok City) fit this criteria-one had not met the pre-TAS criteria and the other, had not passed the TAS criteria. In both cases, the district health teams needed insight into their drug delivery programs in order to improve drug coverage in the subsequent MDA rounds. To inform the subsequent MDA round, a micronarrative survey tool was developed to capture community members' experience with MDA and the social realm where drug delivery and compliance occur. A baseline survey was implemented after the 2013 MDA in endemic communities in both districts using the EPI sampling criteria (n = 806). Compliance in the last MDA was associated with perceived importance of the LF drugs for health (psurvey was performed after the 2014 MDA using the same sampling criteria (n = 811). Reported compliance in the last MDA improved in both districts from 57% to 77% (psurveys were shown to be a valid and effective tool to detect operational issues within MDA programs. District health staff felt ownership of the results, implementing feasible changes to their programs that resulted in significant improvements to coverage and compliance in the subsequent MDA. This kind of implementation research using a micronarrative survey tool could benefit underperforming MDA programs as well as other disease control programs where a deeper understanding is needed to improve healthcare delivery.

  3. Improving patient access to cancer drugs in India: Using economic modeling to estimate a more affordable  drug cost based on measures of societal value

    OpenAIRE

    Lubbe, Martha Susanna; Dranitsaris, George; Truter, Ilse; Sriramanakoppa, Nitin N; Mendonca, Vivian M.

    2011-01-01

    Background: Using multiples of India's per capita gross domestic product (GDP) as the threshold for economic value as suggested by the World Health Organization (WHO), decision analysis modeling was used to estimate a more affordable monthly cost in India for a hypothetical new cancer drug that provides a 3-month survival benefit to Indian patients with metastatic colorectal cancer (mCRC). ...

  4. Global initiative for interdisciplinary approach to improve innovative clinical research and treatment outcomes in geriatrics: biological cell-based targeted drug delivery systems for geriatrics.

    Science.gov (United States)

    Zhumadilov, Zhaxybay

    2013-06-01

    At the intersection of the late 20(th) century and early 21(st) century, a worldwide challenge began to emerge--how can the quality of life be improved for a steadily increasing elderly population. It is well known that elderly patients show increased susceptibility to infections and a higher incidence of co-morbidity rates. Older adults frequently demonstrate pharmacokinetic and pharmacodynamic changes promoting adverse drug reactions and complications. Analysis of world literature and practical observations indicate that new approaches are required in gerontology and geriatric medicine due to recent significant advances in biomedical science. Global interdisciplinary approaches to improve medical science and medical care services for growing elderly population are indicated. This global, interdisciplinary initiative should integrate select, tangible clinical results achieved in leading research centers and universities that are applicable in the field of geriatrics and helpful to geriatricians. Among past scientific and clinically significant study results in the field of biomedicine, one must consider targeted drug delivery systems (DDS), which are designed to minimize drug side effects, increase the efficacy of drugs, and prolong and target drug interactions with particular pathological foci in sick patients. Many review articles focus on various methods of drug encapsulation and pharmacokinetics, but not on developing clinical modalities. This article attempts to further the discussion with researchers and clinicians from various fields, as well as to encourage comprehensive and elderly patient-oriented research focused on clinical implementation of DDS, especially erythrocyte-based DDS.

  5. Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

    Science.gov (United States)

    Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.

    2016-10-01

    Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

  6. Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats.

    Science.gov (United States)

    Zhu, Yuan; Wang, Miaomiao; Zhang, Jiajia; Peng, Wei; Firempong, Caleb Kesse; Deng, Wenwen; Wang, Qilong; Wang, Shicheng; Shi, Feng; Yu, Jiangnan; Xu, Ximing; Zhang, Weiming

    2015-04-01

    This study innovatively prepared an effective capsaicin-loaded liposome, a nanoformulation with fewer irritants, for oral administration. The in vitro and in vivo properties of the liposomal encapsulation were investigated and the potential possibility of oral administration evaluated. The liposomal agent composed of phospholipid, cholesterol, sodium cholate and isopropyl myristate was prepared using film-dispersion method. A level A in vitro-in vivo correlation (IVIVC) was established for the first time, which demonstrated an excellent IVIVC of both formulated and free capsaicin in oral administration. Physicochemical characterizations including mean particle size, zeta (ζ) potential and average encapsulation efficiency of capsaicin-loaded liposome were found to be 52.2 ± 1.3 nm, -41.5 ± 2.71 mv and 81.9 ± 2.43 %, respectively. In vivo, liposomal encapsulation allowed a 3.34-fold increase in relative bioavailability compared to free capsaicin. The gastric mucosa irritation studies indicated that the liposomal system was a safe carrier for oral administration. These results support the fact that capsaicin, an effective drug for the treatment of neuropathic pain, could be encapsulated in liposome for improved oral bioavailability. The excellent IVIVC of capsaicin-loaded liposome could also be a promising tool in liposomal formulation development with an added advantage of reduced animal testing.

  7. Coaxial electrospinning with acetic acid for preparing ferulic acid/zein composite fibers with improved drug release profiles.

    Science.gov (United States)

    Yang, Jian-Mao; Zha, Liu-sheng; Yu, Deng-Guang; Liu, Jianyun

    2013-02-01

    This study investigated drug/zein composite fibers prepared using a modified coaxial electrospinning process. With unspinnable acetic acid as sheath liquid and an electrospinnable co-dissolving solution of zein and ferulic acid (FA) as core fluid, the modified coaxial process could run smoothly and continuously without any clogging. Compared with those from the single-fluid electrospinning process, the FA-loaded zein fibers from the modified process were rounder and possessed higher quality in terms of diameter and distribution, as verified by scanning electron microscopic observations of their surface and cross-section. Differential scanning calorimetry and X-ray diffraction showed that fibers from both processes similarly formed a composite with the FA present in the zein matrix in an amorphous state. The driving force of encapsulation of FA into zein fibers was hydrogen bonding, as evidenced by the attenuated total reflectance Fourier transform infrared spectra. However, in vitro dissolution tests demonstrated that the fibers from the coaxial process exhibited better sustained-release profiles with a smaller initial burst effect and less tailing-off release compared with those from the single process. The modified coaxial electrospinning process is a useful tool for generating nanofibers with higher quality and improved functional performance.

  8. Can mobile phone messages to drug sellers improve treatment of childhood diarrhoea?--A randomized controlled trial in Ghana.

    Science.gov (United States)

    Friedman, Willa; Woodman, Benjamin; Chatterji, Minki

    2015-03-01

    Oral rehydration solution (ORS) and zinc are the recommended treatment in developing countries for the management of uncomplicated diarrhoea in children under five (World Health Organization and UNICEF 2004). However, drug sellers often recommend costly and unnecessary treatments instead. This article reports findings from an experiment to encourage licensed chemical sellers (LCS) in Ghana to recommend ORS and zinc for the management of childhood diarrhoea. The intervention consisted of mobile phone text messages (Short Message Service or SMS) sent to a randomly assigned group of LCS who had been trained on the diarrhoea management protocols recommended by the World Health Organization (WHO). The SMS campaign comprised informational messages and interactive quizzes sent over an 8-week period. The study measured the impact of the SMS messages on both reported and actual practices. Analysis of data from both face-to-face interviews and mystery client visits shows that the SMS intervention improved providers' self-reported practices but not their actual practices. The study also finds that actual practices deviate substantially from reported practices.

  9. Improved drug delivery properties of PVDF membranes functionalized with beta-cyclodextrin--application to guided tissue regeneration in periodontology.

    Science.gov (United States)

    Boschin, F; Blanchemain, N; Bria, M; Delcourt-Debruyne, E; Morcellet, M; Hildebrand, H F; Martel, B

    2006-10-01

    The purpose of this study was to develop a membrane for guided tissue regeneration applicable in periodontology that could release antimicrobial agent during the healing period. Our strategy consisted to graft beta-cyclodextrin (beta-CD), a molecule that is known to form inclusion complexes with a large variety of drugs, onto PVDF membranes. Grafting occurred by using citric acid that provoked a crosslinking reaction of beta-CD, and the resulting polymer was imprisoned into the porous structure of the PVDF membrane. The reaction produced a weight increase of the membrane, the range of which depended on the temperature and on the time of curing applied in the process. The biological behavior of the membranes evaluated by proliferation and vitality tests showed good proliferation and improved activity of L132 epithelial cells on the raw and on the grafted membranes. Doxycyclin (DOX) and chlorhexidine (CHX) were used as antimicrobial agents. Their inclusion into the beta-CD cavity in aqueous solutions was confirmed by NMR spectroscopy. After the impregnation of the membranes with DOX and CHX, their release was studied in vitro in batch type experiments and measured by UV spectrophotometry. Low amounts of DOX and CHX were delivered from the raw membranes within the first few hours of tests. Grafted membranes, however, delivered DOX and CHX in larger quantities within 24 h and 10 days respectively.

  10. Lidocaine self-sacrificially improves the skin permeation of the acidic and poorly water-soluble drug etodolac via its transformation into an ionic liquid.

    Science.gov (United States)

    Miwa, Yasushi; Hamamoto, Hidetoshi; Ishida, Tatsuhiro

    2016-05-01

    Poor transdermal penetration of active pharmaceutical ingredients (APIs) impairs both bioavailability and therapeutic benefits and is a major challenge in the development of transdermal drug delivery systems. Here, we transformed a poorly water-soluble drug, etodolac, into an ionic liquid in order to improve its hydrophobicity, hydrophilicity and skin permeability. The ionic liquid was prepared by mixing etodolac with lidocaine (1:1, mol/mol). Both the free drug and the transformed ionic liquid were characterized by differential scanning colorimetry (DSC), infrared spectroscopy (IR), and saturation concentration measurements. In addition, in vitro skin-permeation testing was carried out via an ionic liquid-containing patch (Etoreat patch). The lidocaine and etodolac in ionic liquid form led to a relatively lower melting point than either lidocaine or etodolac alone, and this improved the lipophilicity/hydrophilicity of etodolac. In vitro skin-permeation testing demonstrated that the Etoreat patch significantly increased the skin permeation of etodolac (9.3-fold) compared with an etodolac alone patch, although an Etoreat patch did not increase the skin permeation of lidocaine, which was consistent with the results when using a lidocaine alone patch. Lidocaine appeared to self-sacrificially improve the skin permeation of etodolac via its transformation into an ionic liquid. The data suggest that ionic liquids composed of approved drugs may substantially expand the formulation preparation method to meet the challenges of drugs which are characterized by poor rates of transdermal absorption.

  11. A Eu3+/Gd3+-EDTA-doped structurally controllable hollow mesoporous carbon for improving the oral bioavailability of insoluble drugs and in vivo tracing

    Science.gov (United States)

    Liu, Jia; Zhao, Yating; Cui, Yu; Yue, Yang; Gao, Yikun; Zhao, Qinfu; Liu, Jie; Wang, Siling

    2016-08-01

    A structurally controllable fluorescence-labeled hollow mesoporous carbon (HMC) was simply prepared to improve the oral bioavailability of insoluble drugs and further trace their delivery process in vivo. The hollow structure was derived from an inverse replica process using mesoporous silica as a template and the fluorescent label was prepared by doping the carboxylated HMC with a confinement of Eu3+/Gd3+-EDTA. The physicochemical properties of the composites were systematically characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and photoluminescence spectra tests prior to studying their effects on drug-release behavior and biodistribution. As a result, the thickness of the carrier’s shell was adjusted from 70 nm to 130 nm and the maximum drug loading was up to 73.6%. The model drug carvedilol (CAR) showed sustained release behavior compared to CAR commercial capsules, and the dissolution rate slowed down as the shells got thicker. AUC0-48h and Tmax were enlarged 2.2 and 6.5 fold, respectively, which demonstrated that oral bioavailability was successfully improved. Bioimaging tests showed that the novel carbon vehicle had a long residence time in the gastrointestinal tract. In short, the newly designed HMC is a promising drug carrier for both oral bioavailability improvement and in vivo tracing.

  12. Nanoparticle mediated P-glycoprotein silencing for improved drug delivery across the blood-brain barrier: a siRNA-chitosan approach.

    Directory of Open Access Journals (Sweden)

    Jostein Malmo

    Full Text Available The blood-brain barrier (BBB, composed of tightly organized endothelial cells, limits the availability of drugs to therapeutic targets in the central nervous system. The barrier is maintained by membrane bound efflux pumps efficiently transporting specific xenobiotics back into the blood. The efflux pump P-glycoprotein (P-gp, expressed at high levels in brain endothelial cells, has several drug substrates. Consequently, siRNA mediated silencing of the P-gp gene is one possible strategy how to improve the delivery of drugs to the brain. Herein, we investigated the potential of siRNA-chitosan nanoparticles in silencing P-gp in a BBB model. We show that the transfection of rat brain endothelial cells mediated effective knockdown of P-gp with subsequent decrease in P-gp substrate efflux. This resulted in increased cellular delivery and efficacy of the model drug doxorubicin.

  13. Ionotropic Cross-linked Carbo-protein Micro Matrix System: An Approach for Improvement of Drug Release, Compaction and Tableting behavior of Losartan Potassium.

    Science.gov (United States)

    Khandai, Madhusmruti; Chakraborty, Santanu; Ghosh, Ashoke Kumar

    2015-01-01

    The aim of the present research work is to develop carbo-protein polymeric complex based sustain release microspheres of losartan potassium and investigate the ability of this dosage form to improve the flowability, compressibility and tableting properties of losartan potassium. The influence of silk sericin, alginate and its blend on various physicochemical parameters and in vitro drug release pattern were studied to optimize the concentration of polymeric blend required for 12 h. sustain release. Optimized batch was subjected to different flowability, compressibility and tableting properties studies to observe the effects of carbo-protein microspheres on flow properties. Results indicated that the concentration of sericin was found to be the main influential factor for prolonged drug release. Different micromeritic studies revealed that the poor flowability and compressibility properties of pure losartan potassium were significantly improved by this algino-sericin microspheric dosage form. Research findings also revealed that plasticity, die filling behavior and tableting properties of the pure drug were significantly improved by this microsphere formulation. So these prospective results concluded that carbo-protein polymeric microspheres helps to sustain the drug release for prolong hours as well as improve the flowability, compressibility and tableting properties of losartan potassium.

  14. Project Self-Esteem: A Parent Involvement Program for Improving Self-Esteem and Preventing Drug and Alcohol Abuse, K-6. Revised.

    Science.gov (United States)

    McDaniel, Sandy; Bielen, Peggy

    This guide presents Project Self-Esteem, a program for improving self-esteem and preventing drug and alcohol abuse in kindergarten through grade 6. Chapter I presents the team leader's guide and discusses introducing the program to the principal, school staff, and parents. Chapter II focuses on kindergarten and includes lessons on being a friend…

  15. Roles of nonpolar and polar intermolecular interactions in the improvement of the drug loading capacity of PEO-b-PCL with increasing PCL content for two hydrophobic Cucurbitacin drugs.

    Science.gov (United States)

    Patel, Sarthak K; Lavasanifar, Afsaneh; Choi, Phillip

    2009-09-14

    Molecular dynamics (MD) simulation was used to study the roles of nonpolar and polar intermolecular interactions in the improvement of the drug loading capacity of poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) with increasing PCL content for two water insoluble anticancer drugs: Cucurbitacin B (CuB) and Cucurbitacin I (CuI). In particular, random binary mixture models containing 10-12 wt % drug and remaining PEO-b-PCL with three different PCL/PEO (w/w) ratios (0.5, 1, and 2) were used to calculate their Flory-Huggins interaction parameters (chi). The MD simulation results show that, for both CuB and CuI, the computed chi decreases (i.e., affinity increases) with increasing PCL/PEO ratio. Such results are consistent with our experimental observation that increasing the PCL/PEO (w/w) ratio from 1 to 4.8 significantly increases the drug loading capacity of micelles formed by PEO-b-PCL for both drugs. Analysis of the energy data shows that increasing affinity (loading) at higher PCL/PEO ratio is attributed to the increase in favorable polar interactions and to the formation of additional hydrogen bonds (H-bonds) between the drugs and the PCL block rather than to the increase in the hydrophobic characteristics of the diblock copolymer as one would normally expect. In fact, the nonpolar intermolecular interactions became more unfavorable at higher PCL/PEO ratio. Analysis of the radial distribution functions of the model mixtures indicates that at high PCL/PEO ratio, multiple H-bond sites on the PCL block interacted with single H-bond sites on the drug molecules. However, at low PCL/PEO ratio, only single H-bonds formed between various H-bond sites on the drug molecules and those of the PCL and PEO blocks. It seems that formation of H-bonds between multiple H-bond sites on the PCL block and single H-bond sites on the drug molecules is responsible for inducing drug/PEO-b-PCL affinity. The finding also explains the experimental observation that release rates

  16. Selective pulmonary artery perfusion for the treatment of primary lung cancer : Improved drug exposure of the lung

    NARCIS (Netherlands)

    van Putte, Bart P.; Grootenboers, Marco; van Boven, Wim-Jan; van Oosterhout, M.; Pasterkamp, Gerard; Folkerts, Gert; Schramel, Franz

    2009-01-01

    Introduction: Selective pulmonary artery perfusion (SPAP) is an experimental drug infusion method for the treatment of lung cancer that aims to achieve more effective T(umour) and lymph N(ode) down-staging. The aim of this experiment was to compare drug uptake of gemcitabine and carboplatin during S

  17. Not to catch but to deter : simple, less intrusive drug and alcohol tests can improve workplace safety

    Energy Technology Data Exchange (ETDEWEB)

    Stastny, P.

    2009-04-15

    Canadian employees who test positive for drug use have access to a wide range of substance counselling and rehabilitation options. As a result of Canadian human right legislation, drug dependence is considered a disability, and Canadian employers are required to accommodate the employee and retain their position when they are deemed fit for work. While Alberta is considered an employee-friendly province, the oil and gas industry has significant hazards that require a lucid and attentive workforce. As a result, Alberta courts approved pre-employment drug testing in a recent court case. The decision involved an employee who tested positive for traces of marijuana. After being fired, the employee filed a complaint. Although the Queen's Bench decided in favour of the employee, the Alberta Court of Appeal stated that the company's pre-employment drug testing policy did not discriminate against the employee on the basis of a disability. Drug use amongst construction workers and employees in the energy industry has now reached upwards of 24 per cent. While urine testing is a commonly used drug testing method, oral fluid testing is now being more widely adopted in industry. Oral fluids can be used to detect recent drug and alcohol use rather than historical use and can be conducted in the presence of a test administrator. It was concluded that the aim of drug and alcohol testing is to deter substance abuse on the job. 3 figs.

  18. Nanocomposite formation between alpha-glucosyl stevia and surfactant improves the dissolution profile of poorly water-soluble drug.

    Science.gov (United States)

    Uchiyama, Hiromasa; Tozuka, Yuichi; Nishikawa, Masahiro; Takeuchi, Hirofumi

    2012-05-30

    The formation of a hybrid-nanocomposite using α-glucosyl stevia (Stevia-G) and surfactant was explored to improve the dissolution of flurbiprofen (FP). As reported previously, the dissolution amount of FP was enhanced in the presence of Stevia-G, induced by the formation of an FP and Stevia-G-associated nanostructure. When a small amount of sodium dodecyl sulfate (SDS) was present with Stevia-G, the amount of dissolved FP was extremely enhanced. This dissolution-enhancement effect was also observed with the cationic surfactant of dodecyl trimethyl ammonium bromide, but not with the non-ionic surfactant of n-octyl-β-D-maltopyranoside. To investigate the dissolution-enhancement effect of Stevia-G/SDS mixture, the pyrene I(1)/I(3) ratio was plotted versus the Stevia-G concentration. The pyrene I(1)/I(3) ratio of Stevia-G/SDS mixture had a sigmoidal curve at lower Stevia-G concentrations compared to the Stevia-G solution alone. These results indicate that the Stevia-G/SDS mixture provides a hydrophobic core around pyrene molecules at lower Stevia-G concentrations, leading to nanocomposite formation between Stevia-G and SDS. The nanocomposite of Stevia-G/SDS showed no cytotoxicity to Caco-2 cells at a mixture of 0.1% SDS and 1% Stevia-G solution, whereas 0.1% SDS solution showed high toxicity. These results suggest that the nanocomposite formation of Stevia-G/SDS may be useful way to enhance the dissolution of poorly water-soluble drugs without special treatment.

  19. Rational drug discovery of HCV helicase inhibitor: Improved docking accuracy with multiple seedings of Autodock Vina and in situ minimization.

    Science.gov (United States)

    Lim, SeeKhai; Othman, Rozana; Yusof, Rohana; Heh, ChoonHan

    2016-11-30

    Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximate 3% of the global populations. Despite the present of several direct antiviral agents in the treatment of hepatitis C, the standard treatment for HCV is accompanied by several drawbacks such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants. To discover potential inhibitors for HCV helicase through an optimized in silico approach. In this study, a homology model (HCV Genotype 3 helicase) was used as the target and screened through a benzopyran-based virtual library. Multiple-seedings of Autodock Vina and in situ minimizations were to account the non-deterministic nature of Autodock Vina search algorithm and binding site flexibility respectively. ADME/T and interaction analysis were also done on the top hits via FAFDRUG3 web server and Discovery Studio 4.5. We developed an improved flow for virtual screening through implementing multiple-seeding screening approach and in situ minimization in the study. With the new docking protocol, the redocked standards have shown better RMSD value in reference to their native conformations. 10 benzopyran-liked compounds with satisfactory physicochemical properties were discovered to be a potential inhibitor of HCV helicase. ZINC38649350 was identified as the most potential inhibitor. 10 potential HCV helicase inhibitors were discovered via a new docking optimization protocol with better docking accuracy. These findings could contribute to the discovery of novel HCV antivirals and serves as an alternative approach of in silico rational drug discovery.

  20. Development of a Novel Milling System Using Supercritical Carbon Dioxide for Improvement of Dissolution Characteristics of Water-Poorly Soluble Drugs.

    Science.gov (United States)

    Fern, Jennifer Chia Wee; Nakamura, Hideya; Watano, Satoru

    2016-01-01

    The aim of this study is to develop a novel milling system using supercritical carbon dioxide (SC-CO2) for the improvement of dissolution characteristics of water-poorly soluble drugs. SC-CO2 possesses high potential in the application of nanotechnology, due to the attractive properties of SC-CO2 fluid such as cheap, inert and non-polluting. In addition, SC-CO2 has density comparable to a liquid, viscosity similar to a gas, and high diffusion capacity. Most of all, carbon dioxide exists as gas in room temperature and pressure, which enables the removal of fluid instantaneously. In this study, a novel method of milling using SC-CO2 was proposed to produce fine-drug particles. SC-CO2 milling was conducted and its performance was compared with the ones by various milling methods such as jet milling, dry milling and wet milling. A comparison on the effect of each milling medium on its milling performance, drug size distribution, and particle morphology was conducted. Operating variables of the SC-CO2 milling system were also investigated to clarify the factors affecting the milling properties and to improve drug release characteristics of water-poorly soluble drugs.

  1. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kostadinova, Radina; Boess, Franziska [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Applegate, Dawn [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Suter, Laura; Weiser, Thomas; Singer, Thomas [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Naughton, Brian [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Roth, Adrian, E-mail: adrian_b.roth@roche.com [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland)

    2013-04-01

    observed in vivo. ► 3D liver co-cultures can detect species-specific drug toxicity observed in vivo. ► This in vitro model may improve assessment of human relevance of preclinical findings.

  2. 我院药品采购管理模块的改进与应用%Improvement and Application of Drug Procurement Management Module in Our Hospital

    Institute of Scientific and Technical Information of China (English)

    吴颖坤; 张健; 沈烽; 刘艳

    2016-01-01

    目的:提高药品周转率和药库工作效率,降低药品库存成本。方法:在对我院药品进行ABC分类法的基础上,改进原有医院信息系统中的药品采购管理模块。通过在模块中增设采购比例系数,实现系统自动生成科学、精确、合理的药品采购计划;通过增加分类筛选功能,结合配送方式以及药品属性分类结果,实现药品分类采购;通过对改进前、后相关指标进行比较,评价改进效果。结果:与改进前比较,改进后我院药品月平均库存金额下降6.44%,周转率提高47.13%(由4.18%升至6.15%),每次采购计划制订时间下降75.00%(由8 h下降为2 h)。结论:药品采购管理模块经改进后,有效减少了药品库存量,提高了药品周转率和药库工作效率。%OBJECTIVE:To improve the drug turnover rate and the work efficiency of drug storehouse,and to reduce the cost of drug storage. METHODS:Based on ABC dynamic classification,original drug procurement management module in HIS was im-proved. Scientific,accurate and reasonable drug procurement plan was generated by the system automatically through setting pro-curement proportion coefficient. Drug procurement by type was achieved through adding classification scanning function,based on distribution mode and drug property classification. Related index were compared before and after improvement to evaluate the ef-fects of the improvement. RESULTS:Compared with before improvement,average monthly inventory amount of drugs in our hos-pital reduced by 6.44%,turnover rate increased by 47.13%(increasing from 4.18% to 6.15%),and the time for developing pro-curement plan decreased by 75.00%(decreasing from 8 h to 2 h). CONCLUSIONS:The improvement of drug procurement man-agement module effectively reduce drug inventory and improve turnover rate of drugs and work efficiency.

  3. Improving introspection to inform free will regarding the choice by healthy individuals to use or not use cognitive enhancing drugs

    Directory of Open Access Journals (Sweden)

    Thaler David S

    2009-06-01

    Full Text Available Abstract A commentary in Nature entitled "Towards responsible use of cognitive-enhancing drugs by the healthy" (Greely et al 2008 Nature 456: 702–705 offers an opportunity to move toward a humane societal appreciation of mind-altering drugs. Using cognitive enhancing drugs as an exemplar, this article presents a series of hypotheses concerning how an individual might learn optimal use. The essence of the proposal is that individuals can cultivate sensitivity to the effects of ever-smaller amounts of psychoactive drugs thereby making harm less likely and benign effects more probable. Four interrelated hypotheses are presented and briefly discussed. 1. Humans can learn to discriminate ever-smaller doses of at least some mind-altering drugs; a learning program can be designed or discovered that will have this outcome. 2. The skill to discriminate drugs and dose can be generalized, i.e. if learned with one drug a second one is easier and so on. 3. Cultivating this skill/knack would be beneficial in leading to choices informed by a more accurate sense of mind-body interactions. 4. From a philosophical point of view learning the effects of ever-smaller doses of psychoactive agents offers a novel path into and to transcend the objective/subjective barrier and the mind/body problem. Whatever the fate of these specific hypotheses, discussion of cognitive enhancing drugs for healthy individuals has the potential to inspire innovative educational and public policy initiatives toward all types of mind-altering drugs and the people who use them.

  4. Do consumers really trust their doctors’ suggestions and drugs they prescribe? : the relationship between perceived risk and trust in consumer buying decisions on prescription drugs, and how pharmaceutical companies can improve consumer’s trust through marketing activities in China

    OpenAIRE

    Jin, Meina

    2016-01-01

    This thesis examines how perceived risk and trust affect consumer’s buying decisions during the process of buying and consuming prescription drugs, and investigates how pharmaceutical companies can improve consumer’s trust by strategically designing and performing their marketing activities in the Chinese pharmaceutical market. Previous literature has generally introduced the overview of consumer buying process and the two important factors that may influence the buying decisions: percei...

  5. Nanoencapsulation of water-soluble drug, lamivudine, using a double emulsion spray-drying technique for improving HIV treatment

    CSIR Research Space (South Africa)

    Tshweu, L

    2013-10-01

    Full Text Available , Nayak, P L (2010) Synthesis of chitosan- polycaprolactone blend for control delivery of ofloxacin drug. Carbohydrate Polymers 79: 106-113. Schafroth, N, Arpagaus, C, Jadhav, U Y, Makne, S, Douroumis, D (2012) Nano and microparticle engineering...

  6. Formulation Strategies to Improve the Bioavailability of Poorly Absorbed Drugs with Special Emphasis on Self-Emulsifying Systems

    OpenAIRE

    Shweta Gupta; Rajesh Kesarla; Abdelwahab Omri

    2013-01-01

    Poorly water-soluble drug candidates are becoming more prevalent. It has been estimated that approximately 60–70% of the drug molecules are insufficiently soluble in aqueous media and/or have very low permeability to allow for their adequate and reproducible absorption from the gastrointestinal tract (GIT) following oral administration. Formulation scientists have to adopt various strategies to enhance their absorption. Lipidic formulations are found to be a promising approach to combat the c...

  7. An improved method for the characterization of supersaturation and precipitation of poorly soluble drugs using pulsatile microdialysis (PMD).

    Science.gov (United States)

    Shah, Kosha B; Patel, Piyush G; Khairuzzaman, Akm; Bellantone, Robert A

    2014-07-01

    In current pharmaceutical drug discovery, most candidates are poorly soluble in water, which can result in poor bioavailability. To overcome this problem, formulations that create supersaturation of the drug are a well-studied alternative. Characterizing the dissolution from these systems is challenging because conventional methods, such as sampling with a syringe then filtering with a 0.2-0.45 μm filter before an HPLC assay, can overestimate the concentration of dissolved drug by allowing nuclei or small precipitated particles to pass, which then dissolve in the HPLC mobile phase. Nuclei and small particles can also cause overestimation of the dissolved concentration when using optical methods. Such overestimations can lead to failure of in vivo prediction of drug bioavailability from supersaturated systems. This paper reports a novel method to determine the free dissolved drug concentration in a dissolution medium using pulsatile microdialysis (PMD). Ibuprofen was used as a model drug for determining precipitation and supersaturation. Supersaturation was induced chemically by changing pH, and also by dissolution/release from an in-house formulation. The adaptation of a previously developed PMD model is summarized, and experimental results comparing dissolved concentrations determined using PMD and direct sampling by syringe and filtering are presented. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective

    Directory of Open Access Journals (Sweden)

    Dillip Angel

    2010-06-01

    Full Text Available Abstract Background To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. Methods The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS and in Ifakara town. Data collection consisted of: 1 yearly censuses of shops selling drugs; 2 collection of monthly data on availability of anti-malarials in public health facilities; and 3 retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data. Results Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008 and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008 of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock, but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock, but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti

  9. Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective.

    Science.gov (United States)

    Alba, Sandra; Hetzel, Manuel W; Goodman, Catherine; Dillip, Angel; Liana, Jafari; Mshinda, Hassan; Lengeler, Christian

    2010-06-15

    To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO) was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu) in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS) and in Ifakara town. Data collection consisted of: 1) yearly censuses of shops selling drugs; 2) collection of monthly data on availability of anti-malarials in public health facilities; and 3) retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data. Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008) and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008) of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock), but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock), but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti-malarial sales) The public health and private retail

  10. Dithranol-loaded lipid-core nanocapsules improve the photostability and reduce the in vitro irritation potential of this drug

    Energy Technology Data Exchange (ETDEWEB)

    Savian, Ana L. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Rodrigues, Daiane [Curso de Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Weber, Julia; Ribeiro, Roseane F. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Motta, Mariana H. [Curso de Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Schaffazick, Scheila R.; Adams, Andréa I.H. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Andrade, Diego F. de; Beck, Ruy C.R. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS 90610-000 (Brazil); and others

    2015-01-01

    Dithranol is a very effective drug for the topical treatment of psoriasis. However, it has some adverse effects such as irritation and stain in the skin that make its application and patient adherence to treatment difficult. The aims of this work were to prepare and characterize dithranol-loaded nanocapsules as well as to evaluate the photostability and the irritation potential of these nanocarriers. Lipid-core nanocapsules containing dithranol (0.5 mg/mL) were prepared by interfacial deposition of preformed polymer. EDTA (0.05%) or ascorbic acid (0.02%) was used as antioxidants. After preparation, dithranol-loaded lipid-core nanocapsules showed satisfactory characteristics: drug content close to the theoretical concentration, encapsulation efficiency of about 100%, nanometric mean size (230–250 nm), polydispersity index below 0.25, negative zeta potential, and pH values from 4.3 to 5.6. In the photodegradation study against UVA light, we observed a higher stability of the dithranol-loaded lipid-core nanocapsules comparing to the solution containing the free drug (half-life times around 4 and 1 h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing EDTA, respectively; half-life times around 17 and 7 h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing ascorbic acid, respectively). Irritation test by HET-CAM method was conducted to evaluate the safety of the formulations. From the results it was found that the nanoencapsulation of the drug decreased its toxicity compared to the effects observed for the free drug. - Highlights: • Strategy to prepare lipid-core nanocapsules containing dithranol • Evaluation of the nanoencapsulation effect on the photostability and irritation • Evaluation of the in vitro release of dithranol-loaded lipid-core nanocapsules.

  11. Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs.

    Science.gov (United States)

    Ni, Jiang; Tian, Fengchun; Dahmani, Fatima Zohra; Yang, Hui; Yue, Deren; He, Shuwang; Zhou, Jianping; Yao, Jing

    2016-11-01

    The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by (1)H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.

  12. A poly(ether-ester) copolymer for the preparation of nanocarriers with improved degradation and drug delivery kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Gagliardi, M., E-mail: mariacristina.gagliardi@iit.it [Center for Micro Bio-Robotics @SSSA, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025 Pontedera (Italy); Bertero, A. [Department of Biology, Unit of Cellular and Developmental Biology, University of Pisa, S.S.12 Abetone e Brennero 4, 56127 Pisa (Italy); Center for Neuroscience and Cognitive Systems @UNITN, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (Italy); Bardi, G. [Center for Bio-Molecular Nanotechnologies @UniLe, Istituto Italiano di Tecnologia, Via Barsanti, 73010 Arnesano (Italy); Bifone, A. [Center for Neuroscience and Cognitive Systems @UNITN, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (Italy)

    2016-02-01

    This paper reports the synthesis and the physicochemical, functional and biological characterisations of nanocarriers made of a novel di-block biodegradable poly(ether-ester) copolymer. This material presents tunable, fast biodegradation rates, but its products are less acidic than those of other biosorbable polymers like PLGA, thus presenting a better biocompatibility profile and the possibility to carry pH-sensitive payloads. A method for the production of monodisperse and spherical nanoparticles is proposed; drug delivery kinetics and blood protein adsorption were measured to evaluate the functional properties of these nanoparticles as drug carriers. The copolymer was labelled with a fluorescent dye for internalisation tests, and rhodamine B was used as a model cargo to study transport and release inside cultured cells. Biological tests demonstrated good cytocompatibility, significant cell internalisation and the possibility to vehiculate non-cell penetrating moieties into endothelial cells. Taken together, these results support the potential use of this nanoparticulate system for systemic administration of drugs. - Highlights: • We propose a novel biodegradable nanocarrier for intracellular drug delivery. • Biodegradation rates can be finely tuned by controlling copolymer composition. • Degradation products are less acidic, thus enabling delivery of pH-sensitive cargoes. • We demonstrate intracellular delivery of a non-cell-penetrating model drug. • No significant membrane damage by the polymer nanocarriers is observed.

  13. Formulation of olfactory-targeted microparticles with tamarind seed polysaccharide to improve nose-to-brain transport of drugs.

    Science.gov (United States)

    Yarragudi, Sasi B; Richter, Robert; Lee, Helen; Walker, Greg F; Clarkson, Andrew N; Kumar, Haribalan; Rizwan, Shakila B

    2017-05-01

    Targeted delivery and retention of drug formulations in the olfactory mucosa, the target site for nose-to-brain drug absorption is a major challenge due to the geometrical complexity of the nose and nasal clearance. Recent modelling data indicates that 10μm-sized microparticles show maximum deposition in the olfactory mucosa. In the present study we tested the hypothesis that 10μm-sized mucoadhesive microparticles would preferentially deposit on, and increase retention of drug on, the olfactory mucosa in a novel 3D-printed human nasal-replica cast under simulated breathing. The naturally occurring mucoadhesive polymer, tamarind seed polysaccharide (TSP) was used to formulate the microparticles using a spray drying technique. Physicochemical properties of microparticles such as size, morphology and mucoadhesiveness was investigated using a combination of laser diffraction, electron microscopy and texture-analysis. Furthermore, FITC-dextrans (5-40kDa) were incorporated in TSP-microparticles as model drugs. Size-dependent permeability of the FITC-dextrans was observed ex vivo using porcine nasal mucosa. Using the human nasal-replica cast, greater deposition of 10μm TSP-microparticles in the olfactory region was observed compared to TSP-microparticles 2μm in size. Collectively, these findings support our hypothesis that 10μm-sized mucoadhesive microparticles can achieve selective deposition and retention of drug in the olfactory mucosa.

  14. AZ17: a new bispecific drug targeting IL-6 and IL-23 with potential clinical use-improves psoriasis in a human xenograft transplantation model

    DEFF Research Database (Denmark)

    Stenderup, Karin; Kjeldsen, Cecilia Rosada; Shanebeck, K

    2015-01-01

    ; widely accepted to be associated with psoriasis. To meet the need for new therapeutics, we aimed to create a clinically relevant bispecific drug, by combining the inhibitory properties of anti-IL-6 and anti-IL-23 antibodies, exhibiting high affinity, high stability and the ability to be produced in high...... variables that were synthesized separately in Escherichia coli. To improve stability and extend pharmacokinetics, a flexible poly-ethylene glycol molecule was used as linker. In preclinical psoriasis models, AZ17 reduced IL-23-induced ear inflammation and improved psoriasis in a xenograft transplantation...... model where psoriasis skin is transplanted onto immune-deficient mice. The data presented here suggest AZ17 to be a promising drug candidate in psoriasis and other inflammatory diseases associated with Th17 cell development....

  15. Improving brain drug targeting through exploitation of the nose-to-brain route: a physiological and pharmacokinetic perspective.

    Science.gov (United States)

    Badhan, R K S; Kaur, M; Lungare, S; Obuobi, S

    2014-01-01

    With an ageing population and increasing prevalence of central-nervous system (CNS) disorders new approaches are required to sustain the development and successful delivery of therapeutics into the brain and CNS. CNS drug delivery is challenging due to the impermeable nature of the brain microvascular endothelial cells that form the blood-brain barrier (BBB) and which prevent the entry of a wide range of therapeutics into the brain. This review examines the role intranasal delivery may play in achieving direct brain delivery, for small molecular weight drugs, macromolecular therapeutics and cell-based therapeutics, by exploitation of the olfactory and trigeminal nerve pathways. This approach is thought to deliver drugs into the brain and CNS through bypassing the BBB. Details of the mechanism of transfer of administrated therapeutics, the pathways that lead to brain deposition, with a specific focus on therapeutic pharmacokinetics, and examples of successful CNS delivery will be explored.

  16. Discovery of Novel Drugs to Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin Pathway in Fracture Repair and Pseudarthrosis

    Science.gov (United States)

    2015-08-01

    neurofibromatosis. 4 To identify agents that inhibit beta-catenin signaling, we undertook a high throughput screen using mesenchymal cells exhibiting...Med 2007, 4:e249. [3] Poon R HH, Wei X, Pan J, and Alman BA: A high throughput screen identifies Nefopam as targeting cell proliferation in β...AWARD NUMBER: W81XWH-13-1-0113 TITLE: Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin

  17. Zebrafish assessment of cognitive improvement and anxiolysis: filling the gap between in vitro and rodent models for drug development.

    Science.gov (United States)

    Levin, Edward D

    2011-01-01

    Zebrafish can provide a valuable animal model to screen potential cognitive enhancing and anxiolytic drugs. They are economical and can provide a relatively quick indication of possible functional efficacy. In as much as they have a complex nervous system and elaborate behavioral repertoire, zebrafish can provide a good intermediate model between in vitro receptor and cell-based assays and classic mammalian models for drug screening. In addition, the variety of molecular tools available in zebrafish makes them outstanding models for helping to determine the neuromolecular mechanisms for psychoactive drugs. However, to use zebrafish as a translational model we must have validated, sensitive and efficient behavioral tests. In a series of studies, our lab has developed tests of cognitive function and stress response, which are sensitive to drug effects in a similar manner as rodent models and humans for cognitive enhancement and alleviating stress response. In particular, the three-chamber task for learning and memory was shown to be sensitive to the cognitive enhancing effects of nicotine and has been useful in helping to determine neural mechanisms crucial for nicotinic-induced cognitive enhancement. The novel tank diving test was shown to be a valid and efficient test of stress response. It is sensitive to the reduction in stress-related behaviors due to the amxiolytic drugs diazepam and buspirone but not chlordiazepoxide. Nicotine also causes stress alleviating effects which can be interpreted as anxiolytic effects. Zebrafish models of behavioral pharmacology can be useful to efficiently screen test compounds for drug development and can be useful in helping to determine the mechanisms crucial for new therapeutic treatments of neurobehavioral impairments.

  18. Students who developed logical reasoning skills reported improved confidence in drug dose calculation: Feedback from remedial maths classes.

    Science.gov (United States)

    Shelton, Chris

    2016-06-01

    The safe administration of drugs is a focus of attention in healthcare. It is regarded as acceptable that a formula card or mnemonic can be used to find the correct dose and fill a prescription even though this removes any requirement for performing the underlying computation. Feedback and discussion in class reveal that confidence in arithmetic skills can be low even when students are able to pass the end of semester drug calculation exam. To see if confidence in the understanding and performance of arithmetic for drug calculations can be increased by emphasising student's innate powers of logical reasoning after reflection. Remedial classes offered for students who have declared a dislike or lack of confidence in arithmetic have been developed from student feedback adopting a reasoning by logical step methodology. Students who gave up two hours of their free learning time were observed to engage seriously with the learning methods, focussing on the innate ability to perform logical reasoning necessary for drug calculation problems. Working in small groups allowed some discussion of the route to the answer and this was followed by class discussion and reflection. The results were recorded as weekly self-assessment scores for confidence in calculation. A self-selecting group who successfully completed the end of semester drug calculation exam reported low to moderate confidence in arithmetic. After four weeks focussing on logical skills a significant increase in self-belief was measured. This continued to rise in students who remained in the classes. Many students hold a negative belief regarding their own mathematical abilities. This restricts the learning of arithmetic skills making alternate routes using mnemonics and memorised steps an attractive alternative. Practising stepwise logical reasoning skills consolidated by personal reflection has been effective in developing student's confidence and awareness of their innate powers of deduction supporting an

  19. Community Impact of Pharmacy-Randomized Intervention to Improve Access to Syringes and Services for Injection Drug Users

    Science.gov (United States)

    Crawford, Natalie D.; Amesty, Silvia; Rivera, Alexis V.; Harripersaud, Katherine; Turner, Alezandria; Fuller, Crystal M.

    2014-01-01

    Objectives: In an effort to reduce HIV transmission among injection drug users (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the Expanded Syringe Access Program by removing the requirement of a prescription. With evidence suggesting pharmacists' ability to expand their public health role, a structural, pharmacy-based…

  20. Drug delivery systems and liver targeting for the improved pharmacotherapy of the hepatitis B virus (HBV) infection.

    Science.gov (United States)

    Cuestas, María L; Mathet, Verónica L; Oubiña, José R; Sosnik, Alejandro

    2010-07-01

    In spite of the progress made in vaccine and antiviral therapy development, hepatitis B virus (HBV) infection is still the most common cause of liver cirrhosis and hepatocellular carcinoma, with more than 400 million people chronically infected worldwide. Antiviral therapy with nucleos(t)ide analogues and/or immunomodulating peptides is the only option to control and prevent the progression of the disease in chronic hepatitis B (CHB)-infected patients. So far, the current antiviral monotherapy remains unsatisfactory because of the low efficacy and the development of drug resistance mutants. Moreover, viral rebound is frequently observed following therapy cessation, since covalent closed circular DNA (cccDNA) is not removed from hepatocytes by antiviral therapy. First, this review describes the current pharmacotherapy for the management of CHB and the new drug candidates being investigated. Then, the challenges in the development of drug delivery systems for the targeting of antiviral drugs to the liver parenchyma are discussed. Finally, perspectives in the design of a more efficient pharmacotherapy to eradicate the virus from the host are addressed.

  1. Integrating risk minimization planning throughout the clinical development and commercialization lifecycle: an opinion on how drug development could be improved

    Directory of Open Access Journals (Sweden)

    Morrato EH

    2015-02-01

    Full Text Available Elaine H Morrato,1 Meredith Y Smith2 1Colorado School of Public Health, University of Colorado, Anschutz Medical Campus, Aurora, CO, 2EMD Serono, Inc, Rockland, MA, USA Abstract: Pharmaceutical risk minimization programs are now an established requirement in the regulatory landscape. However, pharmaceutical companies have been slow to recognize and embrace the significant potential these programs offer in terms of enhancing trust with health care professionals and patients, and for providing a mechanism for bringing products to the market that might not otherwise have been approved. Pitfalls of the current drug development process include risk minimization programs that are not data driven; missed opportunities to incorporate pragmatic methods and market-based insights, outmoded tools and data sources, lack of rapid evaluative learning to support timely adaption, lack of systematic approaches for patient engagement, and questions on staffing and organizational infrastructure. We propose better integration of risk minimization with clinical drug development and commercialization work streams throughout the product lifecycle. We articulate a vision and propose broad adoption of organizational models for incorporating risk minimization expertise into the drug development process. Three organizational models are discussed and compared: outsource/external vendor, embedded risk management specialist model, and Center of Excellence. Keywords: pharmaceuticals, drug development, risk management, organizational design

  2. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

    Science.gov (United States)

    Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

    2017-03-01

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  3. Community Impact of Pharmacy-Randomized Intervention to Improve Access to Syringes and Services for Injection Drug Users

    Science.gov (United States)

    Crawford, Natalie D.; Amesty, Silvia; Rivera, Alexis V.; Harripersaud, Katherine; Turner, Alezandria; Fuller, Crystal M.

    2014-01-01

    Objectives: In an effort to reduce HIV transmission among injection drug users (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the Expanded Syringe Access Program by removing the requirement of a prescription. With evidence suggesting pharmacists' ability to expand their public health role, a structural,…

  4. Community Impact of Pharmacy-Randomized Intervention to Improve Access to Syringes and Services for Injection Drug Users

    Science.gov (United States)

    Crawford, Natalie D.; Amesty, Silvia; Rivera, Alexis V.; Harripersaud, Katherine; Turner, Alezandria; Fuller, Crystal M.

    2014-01-01

    Objectives: In an effort to reduce HIV transmission among injection drug users (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the Expanded Syringe Access Program by removing the requirement of a prescription. With evidence suggesting pharmacists' ability to expand their public health role, a structural, pharmacy-based…

  5. Aqueous coating dispersion (pseudolatex) of zein improves formulation of sustained-release tablets containing very water-soluble drug.

    Science.gov (United States)

    Li, X N; Guo, H X; Heinamaki, J

    2010-05-01

    Zein is an alcohol soluble protein of corn origin that exhibits hydrophobic properties. Pseudolatexes are colloidal dispersions containing spherical solid or semisolid particles less than 1 microm in diameter and can be prepared from any existing thermoplastic water-insoluble polymer. The novel plasticized film-coating pseudolatex of zein was studied in formulation of sustained-release tablets containing very water-soluble drug. Film formation of plasticized aqueous dispersion was compared with film forming properties of plasticized organic solvent system (ethanol) of zein. The water vapor permeability (WVP), water uptake and erosion, and moisture sorption were evaluated with free films. The tablets containing metoprolol tartrate as a model drug were used in pan-coating experiments. Aqueous film coatings plasticized with PEG 400 exhibited very low water uptake. No significant difference in WVP, moisture sorption and erosion were found between aqueous films and organic solvent-based films of zein plasticized with PEG 400. The atomic force microscopy (AFM) images on microstructure of films showed that colloidal particle size of zein in the aqueous films was smaller than that observed in the solvent-based films. In addition, the aqueous-based films were more compact and smoother than the respective solvent-based films. The aqueous zein-coated tablets containing very water-soluble drug (metoprolol tartrate) exhibited clear sustained-release dissolution profiles in vitro, while the respective solvent-based film-coated tablets showed much faster drug release. Furthermore, aqueous zein-coated tablets had lower water absorption at high humidity conditions. In conclusion, the plasticized aqueous dispersion (pseudolatex) of zein can be used for moisture resistant film coating of sustained-release tablets containing very water-soluble drug.

  6. Nanoencapsulation of water-soluble drug, lamivudine, using a double emulsion spray-drying technique for improving HIV treatment

    Energy Technology Data Exchange (ETDEWEB)

    Tshweu, Lesego, E-mail: tshweull@gmail.com [Council for Scientific and Industrial Research, Materials Science and Manufacturing, Polymers and Composites (South Africa); Katata, Lebogang [North West University, Chemistry Department, Faculty of Agriculture, Science and Technology (South Africa); Kalombo, Lonji; Swai, Hulda [Council for Scientific and Industrial Research, Materials Science and Manufacturing, Polymers and Composites (South Africa)

    2013-11-15

    Current treatments available for human immunodeficiency virus, namely antiretrovirals, do not completely eradicate the virus from the body, leading to life-time commitment. Many antiretrovirals suffer drawbacks from toxicity and unpleasant side effects, causing patience non-compliance. To minimize challenges associated with the antiretrovirals, biodegradable nanoparticles used as drug delivery systems hold tremendous potential to enhance patience compliance. The main objective of this work was to load lamivudine (LAM) into poly(epsilon-caprolactone) (PCL) nanoparticles. LAM is a hydrophilic drug with low plasma half-life of 5–7 h and several unpleasant side effects. LAM was nanoencapsulated into PCL polymer via the double emulsion spray-drying method. Formulation parameters such as the effect of solvent, excipient and drug concentration were optimized for the synthesis of the nanoparticles. Spherical nanoparticles with an average size of 215 ± 3 nm and polydispersity index (PDI) of 0.227 ± 0.01 were obtained, when ethyl acetate and lactose were used in the preparation. However, dichloromethane presented sizes larger than 454 ± 11 nm with PDI of more than 0.4 ± 0.05, irrespective of whether lactose or trehalose was used in the preparation. Some of the nanoparticles prepared with trehalose resulted in crystal formation. UV spectroscopy showed encapsulation efficiency ranging from 68 ± 4 to 78 ± 4 % for LAM depending on the starting drug concentration. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the possibility of preparing amorphous PCL nanoparticles containing LAM. Drug release extended for 4 days in pH 1.3, pH 4.5 and pH 6.8. These results indicated that LAM-loaded PCL nanoparticles show promise for controlled delivery.

  7. Nanoencapsulation of water-soluble drug, lamivudine, using a double emulsion spray-drying technique for improving HIV treatment

    Science.gov (United States)

    Tshweu, Lesego; Katata, Lebogang; Kalombo, Lonji; Swai, Hulda

    2013-11-01

    Current treatments available for human immunodeficiency virus, namely antiretrovirals, do not completely eradicate the virus from the body, leading to life-time commitment. Many antiretrovirals suffer drawbacks from toxicity and unpleasant side effects, causing patience non-compliance. To minimize challenges associated with the antiretrovirals, biodegradable nanoparticles used as drug delivery systems hold tremendous potential to enhance patience compliance. The main objective of this work was to load lamivudine (LAM) into poly(epsilon-caprolactone) (PCL) nanoparticles. LAM is a hydrophilic drug with low plasma half-life of 5-7 h and several unpleasant side effects. LAM was nanoencapsulated into PCL polymer via the double emulsion spray-drying method. Formulation parameters such as the effect of solvent, excipient and drug concentration were optimized for the synthesis of the nanoparticles. Spherical nanoparticles with an average size of 215 ± 3 nm and polydispersity index (PDI) of 0.227 ± 0.01 were obtained, when ethyl acetate and lactose were used in the preparation. However, dichloromethane presented sizes larger than 454 ± 11 nm with PDI of more than 0.4 ± 0.05, irrespective of whether lactose or trehalose was used in the preparation. Some of the nanoparticles prepared with trehalose resulted in crystal formation. UV spectroscopy showed encapsulation efficiency ranging from 68 ± 4 to 78 ± 4 % for LAM depending on the starting drug concentration. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the possibility of preparing amorphous PCL nanoparticles containing LAM. Drug release extended for 4 days in pH 1.3, pH 4.5 and pH 6.8. These results indicated that LAM-loaded PCL nanoparticles show promise for controlled delivery.

  8. Orphan drugs

    Directory of Open Access Journals (Sweden)

    Goločorbin-Kon Svetlana

    2013-01-01

    Full Text Available Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. The beginning of orphan drugs development. This problem was first recognized by Congress of the United States of America in January 1983, and when the ”Orphan Drug Act” was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. Conclusion. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs. [Projekat Ministarstva nauke Republike Srbije, br. III 41012

  9. Drugs, nutrients, and phytoactive principles improving the health span of rodent models of human age-related diseases.

    Science.gov (United States)

    Lebel, Michel; Picard, Frédéric; Ferland, Guylaine; Gaudreau, Pierrette

    2012-02-01

    Rodents are often the species of choice to examine the effect of drugs on survival and on the progression of specific diseased tissues. This statement is also true for research laboratories working in the field of nutrition and aging. In addition to diets that can reduce the life expectancy of rodents, such as diabetogenic or high-fat diets, genetically modified rodents exhibiting different accelerated age-associated diseases also provide important biologic tools to decipher the impact of drugs, nutrients, or phytoactive compounds on their health and life span. This review covers some of the chemicals believed to decelerate the appearance of age-related diseases in different rodent models. Such chemicals include antioxidants, anti-inflammatory molecules, modulators of metabolic sensors, calorie restriction mimetics, and vegetal polyphenolic compounds that affect mitochondrial functions, cellular proliferation or differentiation as well as cell functionality.

  10. Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.

    Science.gov (United States)

    Ferrari, Raffaele; Talamini, Laura; Violatto, Martina Bruna; Giangregorio, Paola; Sponchioni, Mattia; Morbidelli, Massimo; Salmona, Mario; Bigini, Paolo; Moscatelli, Davide

    2017-01-03

    Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.

  11. Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

    Science.gov (United States)

    Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

    2017-05-18

    Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Integrating risk minimization planning throughout the clinical development and commercialization lifecycle: an opinion on how drug development could be improved.

    Science.gov (United States)

    Morrato, Elaine H; Smith, Meredith Y

    2015-01-01

    Pharmaceutical risk minimization programs are now an established requirement in the regulatory landscape. However, pharmaceutical companies have been slow to recognize and embrace the significant potential these programs offer in terms of enhancing trust with health care professionals and patients, and for providing a mechanism for bringing products to the market that might not otherwise have been approved. Pitfalls of the current drug development process include risk minimization programs that are not data driven; missed opportunities to incorporate pragmatic methods and market-based insights, outmoded tools and data sources, lack of rapid evaluative learning to support timely adaption, lack of systematic approaches for patient engagement, and questions on staffing and organizational infrastructure. We propose better integration of risk minimization with clinical drug development and commercialization work streams throughout the product lifecycle. We articulate a vision and propose broad adoption of organizational models for incorporating risk minimization expertise into the drug development process. Three organizational models are discussed and compared: outsource/external vendor, embedded risk management specialist model, and Center of Excellence.

  13. Improved Oral Bioavailability of Lacidipine Using Nanosuspension Technology: Inferior in vitro Dissolution and Superior in vivo Drug Absorption versus Lacipil®.

    Science.gov (United States)

    Zhao, Juanhang; Luo, Lei; Fu, Qiang; Guo, Bei; Li, Yun; Geng, Yajie; Wang, Junfeng; Zhang, Tianhong

    2016-01-01

    Improved dissolution is a better way of increasing the oral absorption of lacidipine (LCDP) because it is a BCS II class drug. The purpose of this study is to improve the oral bioavailability of LCDP by applying nanosuspension technology. LCDP nanosuspensions were prepared by a hybrid method of microprecipitation and high pressure homogenization. The effects of the production parameters (shearing rate and time, the stabilizers and their concentrations, homogenization pressure and number of cycles) were investigated to optimize the preparation process. In vitro characterizations (X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy and dissolution measurement) were carried out and an oral pharmacokinetic study was performed in beagle dogs. LCDP was transformed into an amorphous state during the preparation process, and the mean particle size was about 714.0 ± 12.7 nm. The dissolution rate of LCDP nanosuspensions was faster than that of physical mixtures, but slower than that of Lacipil® (the commercial tablet). Regarding the in vivo pharmacokinetics, the key pharmacokinetic parameters (Cmax and AUC0-∞) of the nanosuspensions were statistically significantly higher than those of both the commercial tablet and physical mixtures. So, this is an efficient drug delivery strategy to facilitate the oral administration of LCDP by using nanosuspension technology, and should be generally applicable to many poorly water-soluble drugs with dissolution rate-limited absorption.

  14. Pharmacists' and pharmacy students' ability to identify drug-related problems using TIMER (Tool to Improve Medications in the Elderly via Review).

    Science.gov (United States)

    Lee, Sarah Snyder; Schwemm, Ann K; Reist, Jeffrey; Cantrell, Matthew; Andreski, Michael; Doucette, William R; Chrischilles, Elizabeth A; Farris, Karen B

    2009-05-27

    Determine the effectiveness of TIMER (Tool to Improve Medications in the Elderly via Review) in helping pharmacists and pharmacy students identify drug-related problems during patient medication reviews. In a randomized, controlled study design, geriatric patient cases were sent to 136 pharmacists and 108 third-year pharmacy students who were asked to identify drug related-problems (DRPs) with and without using TIMER. Pharmacists identified more tool-related DRPs using TIMER (p = 0.027). Pharmacy students identified more tool-related DRPs using TIMER in the first case (p = 0.02), but not in the second. TIMER increased the number of DRPs identified by practicing pharmacists and pharmacy students during medication reviews of hypothetical patient cases.

  15. Pharmacists’ and Pharmacy Students’ Ability to Identify Drug-related Problems Using TIMER (Tool to Improve Medications in the Elderly via Review)

    Science.gov (United States)

    Snyder Lee, Sarah; Schwemm, Ann K.; Reist, Jeffrey; Cantrell, Matthew; Andreski, Michael; Doucette, William R.; Chrischilles, Elizabeth A.

    2009-01-01

    Objective Determine the effectiveness of TIMER (Tool to Improve Medications in the Elderly via Review) in helping pharmacists and pharmacy students identify drug-related problems during patient medication reviews. Methods In a randomized, controlled study design, geriatric patient cases were sent to 136 pharmacists and 108 third-year pharmacy students who were asked to identify drug related-problems (DRPs) with and without using TIMER. Results Pharmacists identified more tool-related DRPs using TIMER (p = 0.027). Pharmacy students identified more tool-related DRPs using TIMER in the first case (p = 0.02), but not in the second. Conclusion TIMER increased the number of DRPs identified by practicing pharmacists and pharmacy students during medication reviews of hypothetical patient cases. PMID:19564995

  16. Solubilities of crystalline drugs in polymers: an improved analytical method and comparison of solubilities of indomethacin and nifedipine in PVP, PVP/VA, and PVAc.

    Science.gov (United States)

    Sun, Ye; Tao, Jing; Zhang, Geoff G Z; Yu, Lian

    2010-09-01

    A previous method for measuring solubilities of crystalline drugs in polymers has been improved to enable longer equilibration and used to survey the solubilities of indomethacin (IMC) and nifedipine (NIF) in two homo-polymers [polyvinyl pyrrolidone (PVP) and polyvinyl acetate (PVAc)] and their co-polymer (PVP/VA). These data are important for understanding the stability of amorphous drug-polymer dispersions, a strategy actively explored for delivering poorly soluble drugs. Measuring solubilities in polymers is difficult because their high viscosities impede the attainment of solubility equilibrium. In this method, a drug-polymer mixture prepared by cryo-milling is annealed at different temperatures and analyzed by differential scanning calorimetry to determine whether undissolved crystals remain and thus the upper and lower bounds of the equilibrium solution temperature. The new annealing method yielded results consistent with those obtained with the previous scanning method at relatively high temperatures, but revised slightly the previous results at lower temperatures. It also lowered the temperature of measurement closer to the glass transition temperature. For D-mannitol and IMC dissolving in PVP, the polymer's molecular weight has little effect on the weight-based solubility. For IMC and NIF, the dissolving powers of the polymers follow the order PVP > PVP/VA > PVAc. In each polymer studied, NIF is less soluble than IMC. The activities of IMC and NIF dissolved in various polymers are reasonably well fitted to the Flory-Huggins model, yielding the relevant drug-polymer interaction parameters. The new annealing method yields more accurate data than the previous scanning method when solubility equilibrium is slow to achieve. In practice, these two methods can be combined for efficiency. The measured solubilities are not readily anticipated, which underscores the importance of accurate experimental data for developing predictive models.

  17. Polytherapy with two or more antihypertensive drugs to lower blood pressure in elderly Ontarians. Room for improvement

    Science.gov (United States)

    Campbell, Norman RC; McAlister, Finlay A; Duong-Hua, Minh; Tu, Karen

    2007-01-01

    BACKGROUND: Although guidelines now recommend polytherapy to achieve blood pressure targets, little is know about which antihypertensive drugs are combined in clinical practice. OBJECTIVE: To examine current practices for the coprescribing of antihypertensive agents. METHODS: A population-based cohort study was performed using linked administrative databases on all Ontario residents 66 years of age or older who were newly treated for hypertension between July 1, 1994, and March 31, 2002, and did not have diabetes or other relevant comorbidities. All patients were followed for two years to determine which antihypertensives were prescribed concurrently. RESULTS: Of the 166,018 patients in the described cohort, 1819 (1%) were prescribed a combination therapy tablet as their first-line therapy. The number of patients prescribed antihypertensive polytherapy within the first two years of diagnosis increased from 2071 (21%) of the 9825 hypertensive patients starting treatment in the second half of 1994 to 2578 (37%) of the 6988 hypertensive patients beginning treatment in the first quarter of 2002 (P<0.0001). Overall, 11,003 (27%) of polytherapy prescriptions were for drugs without additive hypotensive effects when combined and this proportion did not change over time. CONCLUSIONS: Although there has been an increase in the use of polytherapy in elderly hypertensive patients without comorbidities in Ontario over the past decade, more than one-quarter of the two drugs prescribed together have not been proven to have additive hypotensive effects. Because this likely contributes to suboptimal blood pressure control rates, future guidelines and educational programs should devote increased attention to the choice of optimal polytherapy combinations. PMID:17703255

  18. Improving the prediction of in-sewer transformation of illicit drug biomarkers by identifying a new modelling framework

    DEFF Research Database (Denmark)

    Ramin, Pedram; Brock, Andreas Libonati; Polesel, Fabio

    -3-β-D-glucuronide; codeine and its metabolite norcodeine; methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP); mephedrone; and tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-Δ9-THC (THCOH), and 11-nor-9-carboxy-Δ9-THC (THCCOOH). All the transformation....... Furthermore, abiotic transformation was found to be the main transformation mechanism for THC (aerobic conditions); mephedrone, methadone, cocaine, ecgonine methyl ester, cocaethylene, THCOH and THCCOOH (anaerobic conditions). By use of the proposed model the uncertainty of predicting illicit drug...

  19. Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia.

    Science.gov (United States)

    Pardo, Bernardo M; Garolera, Maite; Ariza, Mar; Pareto, Deborah; Salamero, Manel; Valles, Vicenç; Delgado, Luis; Alberni, Joan

    2011-12-30

    The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas.

  20. Arginine deiminase: recent advances in discovery, crystal structure, and protein engineering for improved properties as an anti-tumor drug.

    Science.gov (United States)

    Han, Rui-Zhi; Xu, Guo-Chao; Dong, Jin-Jun; Ni, Ye

    2016-06-01

    Arginine deiminase (ADI) is an important arginine-degrading enzyme with wide applications, in particular as an anti-cancer agent for the therapy of arginine-auxotrophic tumors. In recent years, novel ADIs with excellent properties have been identified from various organisms, and crystal structures of ADI were investigated. To satisfy the requirements of potential therapeutic applications, protein engineering has been performed to improve the activity and properties of ADIs. In this mini-review, we systematically summarized the latest progress on identification and crystal structure of ADIs, and protein engineering strategies for improved enzymatic properties, such as pH optimum, K m and k cat values, and thermostability. We also outlined the PEGylation of ADI for improved circulating half-life and immunogenicity, as well as their performance in clinical trials. Finally, perspectives on extracellular secretion and property improvement of ADI were discussed.

  1. Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds.

    Science.gov (United States)

    Ibrahim, Hany S; Eldehna, Wagdy M; Abdel-Aziz, Hatem A; Elaasser, Mahmoud M; Abdel-Aziz, Marwa M

    2014-10-06

    RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 μmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 μmol/mL, respectively.

  2. Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

    Science.gov (United States)

    Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

    2016-01-01

    Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

  3. Genome-wide metabolic model to improve understanding of CD4(+) T cell metabolism, immunometabolism and application in drug design.

    Science.gov (United States)

    Han, Feifei; Li, Gonghua; Dai, Shaoxing; Huang, Jingfei

    2016-02-01

    CD4(+) T cells play a critical role in adaptive immunity and have been well studied in past decades. However, the systematic metabolism features are less clear. Here, we reconstructed the genome-wide metabolic network of naïve CD4(+) T cells, CD4T1670, by integrating transcriptome and metabolism data. We performed simulations for three critical metabolic subsystems (carbohydrate metabolism, fatty acid metabolism and glutaminolysis). The results were consistent with most experimental observations. Furthermore, we found that depletion of either glucose or glutamine did not significantly affect ATP production and biomass, but dramatically unbalanced the metabolic network and increased the release of some inflammation or anti-inflammation related factors, such as lysophosphatidylcholine, leukotriene and hyaluronan. Genome-wide single gene knockout analysis showed that acetyl-CoA carboxylase 1 (ACC1) was essential for T cell activation. We further investigated the role of immunometabolic genes in metabolic network stability, and found that over 25% of them were essential. The results also showed that although PTEN is a well-studied proliferation inhibitor, it was essential for maintaining the stability of CD4 metabolic networks. Finally, we applied CD4T1670 to evaluate the side-effects of certain drugs in preclinical experiments. These results suggested that CD4T1670 would be useful in understanding CD4(+) T cells and drug design systematically.

  4. The Queensland experience of participation in a national drug use evaluation project, Community-acquired pneumonia – towards improving outcomes nationally (CAPTION

    Directory of Open Access Journals (Sweden)

    Tett Susan E

    2009-08-01

    Full Text Available Abstract Background Multicentre drug use evaluations are described in the literature infrequently and usually publish only the results. The purpose of this paper is to describe the experience of Queensland hospitals participating in the Community-Acquired Pneumonia Towards Improving Outcomes Nationally (CAPTION project, specifically evaluating the implementation of this project, detailing benefits and drawbacks of involvement in a national drug use evaluation program. Methods Emergency departments from nine hospitals in Queensland, Australia, participated in CAPTION, a national quality improvement project, conducted in 37 Australian hospitals. CAPTION was aimed at optimising prescribing in the management of Community-Acquired Pneumonia according to the recommendations of the Australian Therapeutic Guidelines: Antibiotic 12th edition. The project involved data collection, and evaluation, feedback of results and a suite of targeted educational interventions including audit and feedback, group presentations and academic detailing. A baseline audit and two drug use evaluation cycles were conducted during the 2-year project. The implementation of the project was evaluated using feedback forms after each phase of the project (audit or intervention. At completion a group meeting with the hospital coordinators identified positive and negative elements of the project. Results Evaluation by hospitals of their participation in CAPTION demonstrated both benefits and drawbacks. The benefits were grouped into the impact on the hospital dynamic such as; improved interdisciplinary working relationships (e.g. between pharmacist and doctor, recognition of the educational/academic role of the pharmacist, creation of ED Pharmacist positions and enhanced involvement with the National Prescribing Service, and personal benefits. Personal benefits included academic detailing training for participants, improved communication skills and opportunities to present at

  5. Re: Pregabalin prescriptions in the United Kingdom - a drug utilisation study of The Health Improvement Network (THIN) primary care database by Asomaning et al

    DEFF Research Database (Denmark)

    Pottegård, A; Tjäderborn, M; Schjerning, O

    2016-01-01

    Aim In Europe, pregabalin is approved for treatment of neuropathic pain, general anxiety disorder (GAD) and as adjunctive therapy for epilepsy. The purpose of this study was to assess utilisation of pregabalin in the UK, including patients with a recorded history of substance abuse, from a large...... general practice database. Methods This observational drug utilisation study (DUS) analysed pregabalin prescription data from the UK Health Improvement Network primary care database between September 2004 and July 2009. Patient demographics, diagnoses (by READ codes) and pregabalin dosing data were...

  6. Improvement in plasma drug activity during the early treatment interval among Tanzanian patients with multidrug-resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Norah D Ndusilo

    Full Text Available Individual pharmacokinetic variability may be common in patients treated for multidrug-resistant tuberculosis (MDR-TB but data are sparse from resource-limited settings and across the early treatment interval.Plasma drug activity, as measured by the TB Drug Activity (TDA assay at 2 and 4 weeks of treatment with a standardized MDR-TB regimen was performed in patients with pulmonary MDR-TB from Tanzania. TDA values were correlated with measures of early treatment outcome including every two week collection of sputum for time-to-positivity (TTP in liquid culture from the MGIT 960 automated system. Patients were evaluated at 24 weeks and those surviving without delayed sputum culture conversion (>8 weeks, culture reversion after previously negative, or weight loss were defined as having a favorable outcome.Twenty-five patients were enrolled with a mean age of 37 ±12 years. All were culture positive from the pretreatment sputum sample with a mean TTP in MGIT of 257 ±134 hours, and the median time to culture conversion on treatment was 6 weeks. Twenty patients (80% had an increase in TDA, with the overall mean TDA at 2 weeks of 2.1 ±0.7 compared to 2.4 ±0.8 at 4 weeks (p = 0.005. At 2 weeks 13 subjects (52% had a TDA value > 2-log killing against their own M. tuberculosis isolate compared to 17 subjects (68% at 4 weeks (McNemar's exact test p = 0.29. An interim treatment outcome was able to be determined in 23 patients (92%, of whom 7 had a poor outcome (30%. An increase in TDA from week 2 to week 4 was associated with favorable outcome, [unadjusted OR = 20.0, 95% CI: 1.61-247.98, exact p = 0.017 and adjusted OR = 19.33, 95% CI: 1.55-241.5, exact p = 0.023].The majority of patients with MDR-TB in Tanzania had an increase in plasma drug activity from week 2 to week 4 of treatment as measured by the TDA assay. Understanding the etiology and full impact of this dynamic may inform therapeutic intervention.

  7. Cyclic RGD peptide-modified liposomal drug delivery system: enhanced cellular uptake in vitro and improved pharmacokinetics in rats

    Directory of Open Access Journals (Sweden)

    Chen Z

    2012-07-01

    Full Text Available Zhongya Chen,1,2 Jiaxin Deng,1,2 Yan Zhao,1,2 Tao Tao1,21National Pharmaceutical Engineering Research Center, 2Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaBackground: Integrins αvβ3 and αvβ5, both of which specifically recognize the Arg-Gly-Asp (RGD motif, are overexpressed on many solid tumors and in tumor neovasculature. Thus, coupling the RGD motif to the liposomal surface for achieving active targeting can be a promising strategy for the treatment of tumors.Methods: Cyclo(Arg-Gly-Asp-D-Phe-Cys (cRGD was covalently coupled with the liposomal membrane surface, followed by coating with poly(ethylene glycol (PEG using the post-insertion technique. The coupling efficiency of cRGD was determined. Doxorubicin as a model anticancer drug was loaded into liposomes using an ammonium sulfate gradient method to investigate the encapsulation efficiency, cellular uptake by the integrin-overexpressing human glioma cell line U87MG in vitro, and pharmacokinetic properties in Sprague-Dawley rats.Results: cRGD was conjugated to the liposomal surface by a thiol-maleimide coupling reaction. The coupling efficiency reached 98%. The encapsulation efficiency of doxorubicin in liposomes was more than 98%. The flow cytometry test result showed that cRGD-modified liposomes (RGD-DXRL-PEG had higher cell uptake by U87MG cells, compared with nontargeted liposomes (DXRL-PEG. The cellular uptake was significantly inhibited in the presence of excess free cRGD. Both the targeted (t1/2 = 24.10 hours and non-targeted (t1/2 = 25.32 hours liposomes showed long circulating properties in rat plasma. The area under the curve of the targeted and nontargeted liposomes was 6.4-fold and 8.3-fold higher than that of doxorubicin solution, respectively.Conclusion: This study indicates preferential targeting and long circulating properties for cRGD-modified liposomes in vivo, which could be used as

  8. An emerging playbook for antibody-drug conjugates: lessons from the laboratory and clinic suggest a strategy for improving efficacy and safety.

    Science.gov (United States)

    Drake, Penelope M; Rabuka, David

    2015-10-01

    Antibody-drug conjugates (ADCs) have become de rigueur for pharmaceutical oncology drug development pipelines. There are more than 40 ADCs undergoing clinical trials and many more in preclinical development. The field has rushed to follow the initial successes of Kadcyla™ and Adcetris™, and moved forward with new targets without much pause for optimization. In some respects, the ADC space has become divided into the clinical realm-where the proven technologies continue to represent the bulk of clinical candidates with a few exceptions-and the research realm-where innovations in conjugation chemistry and linker technologies have suggested that there is much room for improvement in the conventional methods. Now, two and four years after the approvals of Kadcyla™ and Adcetris™, respectively, consensus may at last be building that these two drugs rely on rather unique target antigens that enable their success. It is becoming increasingly clear that future target antigens will require additional innovative approaches. Next-generation ADCs have begun to move out of the lab and into the clinic, where there is a pressing need for continued innovation to overcome the twin challenges of safety and efficacy.

  9. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more.

    Science.gov (United States)

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-07-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized 'Given X, find all associated Ys' query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: 'Find all diseases associated with Bisphenol A'. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation.

  10. Sonication-Based Improvement of the Physicochemical Properties of Guar Gum as a Potential Substrate for Modified Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Siddique Akber Ansari

    2013-01-01

    Full Text Available Guar Gum is a natural polysaccharide that, due to its physicochemical properties, is extensively investigated for biomedical applications as a matrix for modified drug delivery, but it is also used in the food industry as well as in cosmetics. A commercial sample of Guar Gum was sonicated for different periods of time, and the reduction in the average molecular weight was monitored by means of viscometric measurements. At the same time, the rheological behaviour was also followed, in terms of viscoelasticity range, flow curves, and mechanical spectra. Sonicated samples were used for the preparation of gels in the presence of borate ions. The effect of borax on the new samples was investigated by recording mechanical spectra, flow curves, and visible absorption spectra of complexes with Congo Red. The anisotropic elongation, observed in previous studies with tablets of Guar Gum and borax, was remarkably reduced when the sonicated samples were used for the preparation of the gels.

  11. Sonication-based improvement of the physicochemical properties of Guar Gum as a potential substrate for modified drug delivery systems.

    Science.gov (United States)

    Ansari, Siddique Akber; Matricardi, Pietro; Cencetti, Claudia; Di Meo, Chiara; Carafa, Maria; Mazzuca, Claudia; Palleschi, Antonio; Capitani, Donatella; Alhaique, Franco; Coviello, Tommasina

    2013-01-01

    Guar Gum is a natural polysaccharide that, due to its physicochemical properties, is extensively investigated for biomedical applications as a matrix for modified drug delivery, but it is also used in the food industry as well as in cosmetics. A commercial sample of Guar Gum was sonicated for different periods of time, and the reduction in the average molecular weight was monitored by means of viscometric measurements. At the same time, the rheological behaviour was also followed, in terms of viscoelasticity range, flow curves, and mechanical spectra. Sonicated samples were used for the preparation of gels in the presence of borate ions. The effect of borax on the new samples was investigated by recording mechanical spectra, flow curves, and visible absorption spectra of complexes with Congo Red. The anisotropic elongation, observed in previous studies with tablets of Guar Gum and borax, was remarkably reduced when the sonicated samples were used for the preparation of the gels.

  12. Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

    Directory of Open Access Journals (Sweden)

    Guo S

    2016-04-01

    Full Text Available Shujie Guo,1 Kevin Pham,2 Diana Li,2 Scott R Penzak,3 Xiaowei Dong2 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, 3Department of Pharmacotherapy, University of North Texas Health Science Center, Fort Worth, TX, USA Purpose: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability. Materials and methods: In one method, we prepared ritonavir (RTV nanoparticles (NPs by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs. We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules. Results: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability

  13. Improvement in sodium cromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drug.

    Science.gov (United States)

    O'Callaghan, C; Lynch, J; Cant, M; Robertson, C

    1993-01-01

    BACKGROUND--Aerosols generated from metered dose inhalers may be highly charged. The aim of this study was to determine whether lining the walls of a polycarbonate spacer device with an antistatic agent would result in an increase in drug output. The effects of multiple actuations of drug into the spacer device and increasing residence time of drug within the spacer were also determined. METHODS--The amount of sodium cromoglycate contained in particles of various size available for inhalation (per 5 mg actuation) from a 750 ml polycarbonate spacer was determined by impinger measurement and spectrophotometric assay. RESULTS--Lining the spacer with an antistatic agent increased the mean (SD) amount of sodium cromoglycate in particles < 5 microns available for inhalation (per 5 mg actuation) by 244% from (0.59 (0.03) to 1.44 (0.2) mg). When there was a 20 second interval between actuation into the spacer device and inhalation, sodium cromoglycate available for inhalation in particles < 5 micrograms decreased by 67% (from 0.59 (0.03) mg to 0.2 (0.01) mg). Use of the spacer device increased sodium cromoglycate available for inhalation in respirable particles (< 5 microns) by 18% compared with direct delivery by metered dose inhaler. Multiple actuations into the spacer decreased the amount of sodium cromoglycate available for inhalation in particles < 5 microns by 31% after two actuations and 56% after three acutations. CONCLUSIONS--Multiple actuations of sodium cromoglycate into a spacer device before inhalation should be avoided, and inhalation from spacer devices should take place immediately after actuation to ensure maximum dose. Lining of a standard spacer device with an antistatic agent significantly increased output of sodium cromoglycate. This may have implications for improved therapeutic response and drug cost. Images PMID:8346488

  14. The Effectiveness of Cognitive Behavioral Therapy on Increasing of Self-Efficacy and Improving of Addiction Symptoms among Drug Dependency Patients

    Directory of Open Access Journals (Sweden)

    Hamid Kamarzarin

    2012-08-01

    Full Text Available Introduction: The aim of this study was to determine the effectiveness of cognitive behavior therapy on increasing of self efficacy and improving of addiction symptoms among drug dependency patients. Method: For this purpose, 90 substance abusers were selected of private addiction center, Central Prison and drop in center by using of random sampling, and they were divided into two experimental (45 subjects and witness groups (45 subjects randomly. The members of experimental group were under 12 sessions of cognitive behavioral therapy by Carol method, and control group only have taken Methadone and other physical drugs. All participants at the beginning of research, during the study (after three months and three months after treatment completed self-efficacy questionnaire and Maudsley addiction profile (Map by a psychologist were assessed. The symptoms of addiction recovery and addiction treatment process. Results: Analysis of covariance indicated the treatment effectiveness and its maintenance on increasing of efficacy and reducing of the symptoms of Maudsley addiction profile. Conclusion: Cognitive behavior therapy is effective to increase self-efficacy and improve symptoms in substance abusers.

  15. A simple green route to obtain poly(vinyl alcohol) electrospun mats with improved water stability for use as potential carriers of drugs.

    Science.gov (United States)

    López-Córdoba, Alex; Castro, Guillermo R; Goyanes, Silvia

    2016-12-01

    Poly(vinyl alcohol) (PVA) is a hydrophilic, biocompatible and nontoxic polymer. However, because of its low water-resistance, some applications for PVA-based materials are limited (e.g., drug delivery systems and wound dressings). In the current work, PVA mats containing tetracycline hydrochloride (TC) were successfully developed by electrospinning. In order to improve the water stability of the systems, the cross-linking of the PVA matrix was induced by citric acid (CA) addition together with heating treatments (150°C or 190°C for 3min). TC presence led to a strong increase in the electrical conductivity of the blends and as a result, fibers with about 44% lower diameter (270nm) than that of the corresponding unloaded mats (485nm) were obtained. Laser scanning confocal microscopy images indicated that TC was well distributed along the PVA nanofibers. The mats were evaluated by FTIR, which revealed chemical interactions between PVA hydroxyl groups and CA carboxylic ones. The treatment at 150°C for 3min proved to be the more suitable for the preparation of TC-containing mats with improved water resistance, maintaining the TC antimicrobial activity against both Escherichia coli and Staphylococcus aureus almost unaltered. These mats showed a burst release of TC, giving around 95% of the drug within the first hour of immersion in water.

  16. Novel pectin-based nanoparticles prepared from nanoemulsion templates for improving in vitro dissolution and in vivo absorption of poorly water-soluble drug.

    Science.gov (United States)

    Burapapadh, Kanokporn; Takeuchi, Hirofumi; Sriamornsak, Pornsak

    2012-10-01

    The purpose of this study was to improve in vitro dissolution and in vivo absorption of itraconazole (ITZ), a poorly water-soluble drug, by means of novel pectin-based nanoparticles prepared from nanoemulsion templates. Nanoemulsion templates were prepared by a high-pressure homogenization using pectin (i.e., 0.5-3.0%w/w low-methoxyl pectin (LMP), amidated low-methoxyl pectin (ALMP), or high-methoxyl pectin (HMP)) as an emulsifier and chloroform as an oil phase. HMP provided good oil-in-water emulsions with ITZ loaded in the oil phase. The chloroform in nanoemulsions was then removed to produce the suspensions of nanoparticles dispersed in water phase. After lyophilization, the dried core-shell nanoparticles with good properties in terms of redispersibility, dissolution, and stability were obtained. The alteration of ITZ crystallinity was clearly observed from powder X-ray diffractogram while no interaction between ITZ and pectin was found in the nanoparticles. The ITZ-loaded nanoparticles showed high percent drug dissolved, especially those prepared from HMP, and could maintain their good dissolution properties even after 6-month storage. The in vivo absorption study in fasted rats demonstrated that pectin-based nanoparticles prepared from nanoemulsion templates could improve absorption of ITZ, that is, 1.3-fold higher than the ITZ commercial product (pin vivo plasma profile. These findings suggested that HMP-based nanoparticles seem to be a promising formulation due to their high AUC(0-24h) and C(max).

  17. Polysaccharides as Bacterial Antiadhesive Agents and "Smart" Constituents for Improved Drug Delivery Systems Against Helicobacter pylori Infection.

    Science.gov (United States)

    Menchicchi, Bianca; Hensel, Andreas; Goycoolea, Francisco M

    2015-01-01

    The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context

  18. An improved cryopreservation method for porcine buccal mucosa in ex vivo drug permeation studies using Franz diffusion cells.

    Science.gov (United States)

    Amores, Sonia; Domenech, José; Colom, Helena; Calpena, Ana C; Clares, Beatriz; Gimeno, Álvaro; Lauroba, Jacinto

    2014-08-18

    The use of isolated animal models to assess percutaneous absorption of molecules is frequently reported. The porcine buccal mucosa has been proposed as a substitute for the buccal mucosa barrier on ex vivo permeability studies avoiding unnecessary sacrifice of animals. But it is not always easy to obtain fresh buccal mucosa. Consequently, human and porcine buccal mucosa is sometimes frozen and stored in liquid nitrogen, but this procedure is not always feasible. One cheaper and simpler alternative is to freeze the buccal mucosa of freshly slaughtered pigs in a mechanical freezer, using DMSO and albumin as cryoprotective agents. This study compared the ex vivo permeability parameters of propranolol hydrochloride through porcine buccal mucosa using a Franz diffusion cell system and HPLC as detection method. The freezing effects on drug permeability parameters were evaluated. Equally histological studies were performed. Furthermore, the use of the parameter transmucosal water loss (TMWL) as an indicator of the buccal mucosa integrity was evaluated just as transepidermal water loss (TEWL) is utilized for skin integrity. The results showed no difference between fresh and frozen mucosal flux, permeability coefficient or lag time of propranolol. However, statistical significant difference in TMWL between fresh and frozen mucosa was observed.

  19. Beyond Agar: Gel Substrates with Improved Optical Clarity and Drug Efficiency and Reduced Autofluorescence for Microbial Growth Experiments

    Science.gov (United States)

    McElfresh, Cameron; Wong, Lily R.

    2015-01-01

    Agar, a seaweed extract, has been the standard support matrix for microbial experiments for over a century. Recent developments in high-throughput genetic screens have created a need to reevaluate the suitability of agar for use as colony support, as modern robotic printing systems now routinely spot thousands of colonies within the area of a single microtiter plate. Identifying optimal biophysical, biochemical, and biological properties of the gel support matrix in these extreme experimental conditions is instrumental to achieving the best possible reproducibility and sensitivity. Here we systematically evaluate a range of gelling agents by using the yeast Saccharomyces cerevisiae as a model microbe. We find that carrageenan and Phytagel have superior optical clarity and reduced autofluorescence, crucial for high-resolution imaging and fluorescent reporter screens. Nutrient choice and use of refined Noble agar or pure agarose reduce the effective dose of numerous selective drugs by >50%, potentially enabling large cost savings in genetic screens. Using thousands of mutant yeast strains to compare colony growth between substrates, we found no evidence of significant growth or nutrient biases between gel substrates, indicating that researchers could freely pick and choose the optimal gel for their respective application and experimental condition. PMID:26070672

  20. Beyond Agar: Gel Substrates with Improved Optical Clarity and Drug Efficiency and Reduced Autofluorescence for Microbial Growth Experiments.

    Science.gov (United States)

    Jaeger, Philipp A; McElfresh, Cameron; Wong, Lily R; Ideker, Trey

    2015-08-15

    Agar, a seaweed extract, has been the standard support matrix for microbial experiments for over a century. Recent developments in high-throughput genetic screens have created a need to reevaluate the suitability of agar for use as colony support, as modern robotic printing systems now routinely spot thousands of colonies within the area of a single microtiter plate. Identifying optimal biophysical, biochemical, and biological properties of the gel support matrix in these extreme experimental conditions is instrumental to achieving the best possible reproducibility and sensitivity. Here we systematically evaluate a range of gelling agents by using the yeast Saccharomyces cerevisiae as a model microbe. We find that carrageenan and Phytagel have superior optical clarity and reduced autofluorescence, crucial for high-resolution imaging and fluorescent reporter screens. Nutrient choice and use of refined Noble agar or pure agarose reduce the effective dose of numerous selective drugs by >50%, potentially enabling large cost savings in genetic screens. Using thousands of mutant yeast strains to compare colony growth between substrates, we found no evidence of significant growth or nutrient biases between gel substrates, indicating that researchers could freely pick and choose the optimal gel for their respective application and experimental condition.

  1. Founding an adverse drug reaction (ADR) network: a method for improving doctors spontaneous ADR reporting in a general hospital.

    Science.gov (United States)

    Goldstein, Lee Hilary; Berlin, Maya; Saliba, Walid; Elias, Mazen; Berkovitch, Matitiyahu

    2013-11-01

    Adverse drug reactions (ADR) are underreported by doctors despite numerous efforts. We aimed to determine if establishing an "ADR reporting doctor's network" within a hospital would increase the quantity of ADRs reported by hospital doctors. One hundred hospital doctors joined the network. Email reminders were sent to network members during the 1 year study period, conveying information about ADRs reported, amusingly and pleasantly reminding them to report ADRs in minimal detail, by phone, email, text message or mail to the Clinical Pharmacology Unit, who would further complete the report. A total of 114 ADRs were reported during the study period in comparison to 48, 26, and 17 in the previous 3 years (2008, 2009, 2010, respectively). In the 3 years prior, doctors reported 41.7% of the reported ADRs whereas in the study period, doctors reported 74.3% of ADRs (P reports. Ninety seven percent of doctors' reports were of ADR network members. Thirty-four (34%) network members reported an ADR during the study period and 31 of the 34 reporters had never reported ADRs before becoming network members. Establishing an ADR network of doctors substantially increases ADR reporting amongst its members.

  2. Role of health education and self-action plan in improving the drug compliance in bronchial asthma

    Directory of Open Access Journals (Sweden)

    Gajanan S Gaude

    2014-01-01

    Full Text Available Background: Considering the prevalence and associated burden of disease due to bronchial asthma, it is mandatory to obtain an optimal control of the disease and to improve outcomes for these patients. But it has been observed that there is very poor adherence to the inhalational therapy which leads to the suboptimal control of the disease. Objectives of the Study: To study the adherence for aerosol therapy in bronchial asthma patients and to assess the impact of health education and self-action plan in improving the compliance to the therapy. Methodology: A prospective study was done in a total of 500 bronchial asthma patients over a period of 2 years. Once included in the study, the patients were followed-up for a total of 12 weeks for calculation of nonadherence to the aerosol therapy. In nonadherent patients, we employed various health education strategies to improve the compliance in these cases. Results: A total of 500 patients of bronchial asthma who were started on aerosol therapy over duration of 2 years were included in the study. At the end of 12 weeks, it was observed that, only 193 patients (38.6% had regular compliance and 307 patients (61.4% were noncompliant to aerosol therapy as prescribed for bronchial asthma. Factors that were associated with poor compliance were: Lower educational level status, poor socioeconomic status, cumbersome regimens, dislike of medication, and distant pharmacies. Nondrug factors that reduced the compliance were: Fears about side effects, anger about condition or its treatment, forgetfulness or complacency, and patient′s ill attitudes toward health. After employing the various strategies for improving the compliance in these patients, the compliance increased in 176 patients (57.3% among the earlier defaulted patients, while the remaining 131 patients (42.7% were found to be noncompliant even after various educational techniques. Conclusion: Noncompliance in asthma management is a fact of life and no

  3. Can Improving Knowledge of Antibiotic-Associated Adverse Drug Events Reduce Parent and Patient Demand for Antibiotics?

    Directory of Open Access Journals (Sweden)

    Rebecca M. Roberts

    2015-01-01

    Full Text Available Background: According to the Centers for Disease Control and Prevention, at least 2 million people are infected and 23,000 die each year in the United States as a result of antibiotic-resistant bacterial infections. Antibiotic use is the most important factor contributing to antibiotic resistance and overuse is common, especially for upper respiratory tract infections. There is a perception among the public, as well as some health care providers, that antibiotics are harmless. We conducted formative research to explore patient and parent knowledge and attitudes relating to antibiotic use and adverse drug events (ADEs. Methods: Six computer-assisted telephone focus groups were conducted in October and November 2010 with adult patients and mothers of young children. The focus groups were developed to engage participants in discussion about their knowledge and attitudes regarding antibiotic resistance and ADEs associated with antibiotic use. Results: Nearly all mothers were familiar with the possibility of “side effects” with prescription medications, including antibiotics. However, very few mothers were familiar with severe antibiotic-associated ADEs and nearly all felt strongly that this information should be shared with parents at the time a prescription is recommended or written for their child. Adult participants did not believe that the potential for ADEs was a significant issue for adults and most reported never discussing the potential for adverse events with their provider. Conclusions: Parents were receptive to appropriate antibiotic use messaging around ADEs. We learned that ADE messages did not resonate with adults in the same way they did with mothers of young children.

  4. Can Improving Knowledge of Antibiotic-Associated Adverse Drug Events Reduce Parent and Patient Demand for Antibiotics?

    Directory of Open Access Journals (Sweden)

    Rebecca M. Roberts

    2015-01-01

    Full Text Available Background: According to the Centers for Disease Control and Prevention, at least 2 million people are infected and 23,000 die each year in the United States as a result of antibiotic-resistant bacterial infections. Antibiotic use is the most important factor contributing to antibiotic resistance and overuse is common, especially for upper respiratory tract infections. There is a perception among the public, as well as some health care providers, that antibiotics are harmless. We conducted formative research to explore patient and parent knowledge and attitudes relating to antibiotic use and adverse drug events (ADEs. Methods: Six computer-assisted telephone focus groups were conducted in October and November 2010 with adult patients and mothers of young children. The focus groups were developed to engage participants in discussion about their knowledge and attitudes regarding antibiotic resistance and ADEs associated with antibiotic use. Results: Nearly all mothers were familiar with the possibility of “side effects” with prescription medications, including antibiotics. However, very few mothers were familiar with severe antibiotic-associated ADEs and nearly all felt strongly that this information should be shared with parents at the time a prescription is recommended or written for their child. Adult participants did not believe that the potential for ADEs was a significant issue for adults and most reported never discussing the potential for adverse events with their provider. Conclusions: Parents were receptive to appropriate antibiotic use messaging around ADEs. We learned that ADE messages did not resonate with adults in the same way they did with mothers of young children.

  5. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Kids Drug Use Hurts Unborn Children Drug Use Hurts Your Health Drug Use Hurts ... Find Treatment/Rehab Resources Prevent Drug Use Help Children and Teens Stay Drug-Free Talking to Kids ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  7. Why a Combination of WP 631 and Epo B is an Improvement on the Drugs Singly - Involvement in the Cell Cycle and Mitotic Slippage.

    Science.gov (United States)

    Bukowska, Barbara; Rogalska, Aneta; Forma, Ewa; Brys, Magdalena; Marczak, Agnieszka

    2016-01-01

    Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

  8. Implementation of cooperative learning through collaboration with foreign lecturer to improve students' understanding and soft skills in the course of drug delivery system

    Science.gov (United States)

    Syukri, Yandi; Nugroho, Bambang Hernawan

    2017-03-01

    The course of Drug Delivery Systems is an elective that supports the development of new products in pharmaceutical industry. The existing learning process has been in the form of one-direction face-to-face lecturing. During the lecture, students find it difficult to follow or understand the materials, so they become passive. Also, class effectiveness is low because it cannot develop students' active participation during the learning process. To improve the learning outcomes and to achieve the desired competence, innovations in the learning process should be attempted. This learning model aimed to improve students' understanding of and soft skills in the course of Drug Delivery Systems through a cooperative learning method and collaboration with foreign lecturers. The order of cooperative learning included explaining the desired learning outcomes of each topic, providing reading materials for students to learn when preparing their papers, instructing students to work on group assignments and to help each other to master the lesson through question-answer sessions and discussions among group members, encouraging group presentations, and evaluating through quizzes. The foreign lecturers played a role in enriching teaching materials and providing an international class atmosphere. The students' hard skills assessed from the quiz, midterm exam, and final semester exam showed a minimum score of 70 > 80% in the quiz and final semester exam components, while the midterm exam value with a minimum of 70 > 80% was only 6%. The assessment of soft skills obtained from the students' independence in constructing knowledge to complete assignments and resolve problems indicated such outcomes as each group's better ability to access relevant journals, their active participation in group discussions, discipline to submit assignments, discipline to be punctual, and good communication skills. It can be concluded that cooperative learning method could improve the soft skills of students

  9. Improving prescribing of antihypertensive and cholesterol-lowering drugs: a method for identifying and addressing barriers to change

    Directory of Open Access Journals (Sweden)

    Flottorp Signe

    2004-09-01

    Full Text Available Abstract Background We describe a simple approach we used to identify barriers and tailor an intervention to improve pharmacological management of hypertension and hypercholesterolaemia. We also report the results of a post hoc exercise and survey we carried out to evaluate our approach for identifying barriers and tailoring interventions. Methods We used structured reflection, searched for other relevant trials, surveyed general practitioners and talked with physicians during pilot testing of the intervention. The post hoc exercise was carried out as focus groups of international researchers in the field of quality improvement in health care. The post hoc survey was done by telephone interviews with physicians allocated to the experimental group of a randomised trial of our multifaceted intervention. Results A wide range of barriers was identified and several interventions were suggested through structured reflection. The survey led to some adjustments. Studying other trials and pilot testing did not lead to changes in the design of the intervention. Neither the post hoc focus groups nor the post hoc survey revealed important barriers or interventions that we had not considered or included in our tailored intervention. Conclusions A simple approach to identifying barriers to change appears to have been adequate and efficient. However, we do not know for certain what we would have gained by using more comprehensive methods and we do not know whether the resulting intervention would have been more effective if we had used other methods. The effectiveness of our multifaceted intervention is under evaluation in a randomised controlled trial.

  10. Curcumin-coordinated nanoparticles with improved stability for reactive oxygen species-responsive drug delivery in lung cancer therapy

    Science.gov (United States)

    Luo, Cheng-Qiong; Xing, Lei; Cui, Peng-Fei; Qiao, Jian-Bin; He, Yu-Jing; Chen, Bao-An; Jin, Liang; Jiang, Hu-Lin

    2017-01-01

    Background The natural compound curcumin (Cur) can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS)-responsive nanoparticle using the interaction between boronic acid and Cur. Materials and methods We synthesized a highly biocompatible 4-(hydroxymethyl) phenylboronic acid (HPBA)-modified poly(ethylene glycol) (PEG)-grafted poly(acrylic acid) polymer (PPH) and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC) based on the interaction between boronic acid and Cur. The mean diameter of the Cur-coordinated PPHC nanoparticle was 163.8 nm and its zeta potential was −0.31 mV. The Cur-coordinated PPHC nanoparticle improved Cur stability in physiological environment and could timely release Cur in response to hydrogen peroxide (H2O2). PPHC nanoparticles demonstrated potent antiproliferative effect in vitro in A549 cancer cells. Furthermore, the viability of cells treated with PPHC nanoparticles was significantly increased in the presence of N-acetyl-cysteine (NAC), which blocks Cur release through ROS inhibition. Simultaneously, the ROS level measured in A549 cells after incubation with PPHC nanoparticles exhibited an obvious downregulation, which further proved that ROS depression indeed influenced the therapeutic effect of Cur in PPHC nanoparticles. Moreover, pretreatment with phosphate-buffered saline (PBS) significantly impaired the cytotoxic effect of Cur in A549 cells in vitro while causing less damage to the activity of Cur in PPHC nanoparticle. Conclusion The Cur-coordinated nanoparticles developed in this study improved Cur stability, which could further release Cur in a ROS-dependent manner in cancer cells. PMID:28182160

  11. Improving the drug delivery characteristics of graphene oxide based polymer nanocomposites through the “one-pot” synthetic approach of single-electron-transfer living radical polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Peng; Liu, Meiying; Tian, Jianwen; Deng, Fengjie [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wang, Ke [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China); Xu, Dazhuang [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Liu, Liangji [Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006 (China); Zhang, Xiaoyong, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: weiyen@tsinghua.edu.cn [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China)

    2016-08-15

    Graphical abstract: The PEGylated graphene oxides with high water dispersibility, good biocompatibility as well as high drug loading capability were fabricated via “one-pot” SET-LRP. - Highlights: • Surface modification of graphene oxide with polymers. • One-pot single-electron-transfer living radical polymerization. • Improving drug delivery characteristics. • The synthetic approach is rather simple, universal and effective. - Abstract: Graphene oxide (GO) based polymer nanocomposites have attracted extensive research interest recently for their outstanding physicochemical properties and potential applications. However, surface modification of GO with synthetic polymers has demonstrated to be trouble for most polymerization procedures are occurred under non-aqueous solution, which will in turn lead to the restacking of GO. In this work, a facile and efficient “one-pot” strategy has been developed for surface modification of GO with synthetic polymers through single-electron-transfer living radical polymerization (SET-LRP). The GO based polymer nanocomposites were obtained via SET-LRP in aqueous solution using poly(ethylene glycol) methyl ether methacrylate (PEGMA) as the monomer and 11-bromoundecanoic acid as the initiator, which could be effectively adsorbed on GO through hydrophobic interaction. The successful preparation of GO based polymer nanocomposites was confirmed by a series of characterization techniques such as {sup 1}H nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. The resultant products exhibit high water disperisibility, excellent biocompatibility and high efficient drug loading capability, making these PEGylated GO nanocomposites promising candidates for biomedical applications.

  12. Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

    Science.gov (United States)

    Vasconcelos, Aimee; Vega, Estefania; Pérez, Yolanda; Gómara, María J; García, María Luisa; Haro, Isabel

    2015-01-01

    In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. PMID:25670897

  13. Development of a fast high performance liquid chromatographic screening system for eight antidiabetic drugs by an improved methodology of in-silico robustness simulation.

    Science.gov (United States)

    Mokhtar, Hatem I; Abdel-Salam, Randa A; Haddad, Ghada M

    2015-06-19

    Robustness of RP-HPLC methods is a crucial method quality attribute which has gained an increasing interest throughout the efforts to apply quality by design concepts in analytical methodology. Improvement to design space modeling approaches to represent method robustness was the goal of many previous works. Modeling of design spaces regarding to method robustness fulfils quality by design essence of ensuring method validity throughout the design space. The current work aimed to describe an improvement to robustness modeling of design spaces in context of RP-HPLC method development for screening of eight antidiabetic drugs. The described improvement consisted of in-silico simulation of practical robustness testing procedures thus had the advantage of modeling design spaces with higher confidence in estimated of method robustness. The proposed in-silico robustness test was performed as a full factorial design of simulated method conditions deliberate shifts for each predicted point in knowledge space with modeling error propagation. Design space was then calculated as zones exceeding a threshold probability to pass the simulated robustness testing. Potential design spaces were mapped for three different stationary phases as a function of gradient elution parameters, pH and ternary solvent ratio. A robust and fast separation for the eight compounds within less than 6 min was selected and confirmed through experimental robustness testing. The effectiveness of this approach regarding definition of design spaces with ensured robustness and desired objectives was demonstrated.

  14. Improved small molecule drug release from in situ forming poly(lactic-co-glycolic acid) scaffolds incorporating poly(β-amino ester) and hydroxyapatite microparticles.

    Science.gov (United States)

    Fisher, Paul D; Palomino, Pablo; Milbrandt, Todd A; Hilt, J Zach; Puleo, David A

    2014-01-01

    In situ forming implants are an attractive choice for controlled drug release into a fixed location. Currently, rapidly solidifying solvent exchange systems suffer from a high initial burst, and sustained release behavior is tied to polymer precipitation and degradation rate. The present studies investigated addition of hydroxyapatite (HA) and drug-loaded poly(β-amino ester) (PBAE) microparticles to in situ forming poly(lactic-co-glycolic acid) (PLGA)-based systems to prolong release and reduce burst. PBAEs were synthesized, imbibed with simvastatin (osteogenic) or clodronate (anti-resorptive), and then ground into microparticles. Microparticles were mixed with or without HA into a PLGA solution, and the mixture was injected into buffer, leading to precipitation and creating solid scaffolds with embedded HA and PBAE microparticles. Simvastatin release was prolonged through 30 days, and burst release was reduced from 81 to 39% when loaded into PBAE microparticles. Clodronate burst was reduced from 49 to 32% after addition of HA filler, but release kinetics were unaffected after loading into PBAE microparticles. Scaffold dry mass remained unchanged through day 15, with a pronounced increase in degradation rate after day 30, while wet scaffolds experienced a mass increase through day 25 due to swelling. Porosity and pore size changed throughout degradation, likely due to a combination of swelling and degradation. The system offers improved release kinetics, multiple release profiles, and rapid solidification compared to traditional in situ forming implants.

  15. The combination of glycerol metabolic engineering and drug resistance marker-aided genome shuffling to improve very-high-gravity fermentation performances of industrial Saccharomyces cerevisiae.

    Science.gov (United States)

    Wang, Pin-Mei; Zheng, Dao-Qiong; Liu, Tian-Zhe; Tao, Xiang-Lin; Feng, Ming-Guang; Min, Hang; Jiang, Xin-Hang; Wu, Xue-Chang

    2012-03-01

    A challenge associated with the ethanol productivity under very-high-gravity (VHG) conditions, optimizing multi-traits (i.e. byproduct formation and stress tolerance) of industrial yeast strains, is overcome by a combination of metabolic engineering and genome shuffling. First, industrial strain Y12 was deleted with a glycerol exporter Fps1p and hetero-expressed with glyceraldehydes-3-phosphate dehydrogenase, resulting in the modified strain YFG12 with lower glycerol yield. Second, YFG12 was subjected to three rounds of drug resistance marker-aided genome shuffling to increase its ethanol tolerance, and the best shuffled strain TS5 was obtained. Compared with wild strain Y12, shuffled strain TS5 not only decreased glycerol formation by 14.8%, but also increased fermentation rate and ethanol yield by 3.7% and 7.6%, respectively. Moreover, the system of genetic modification and Cre/loxP in aid of three different drug-resistance markers presented in the study significantly improved breeding efficiency and will facilitate the application of breeding technologies in prototrophic industrial microorganisms.

  16. Improvement of the mechanical properties of an {alpha}-TCP cement by the addition of a polymeric drug containing salicylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Ginebra, M.P.; Rilliard, A.; Fernandez, E.; Planell, J.A. [Universidad Politecnica de Cataluna, Barcelona (Spain). Dept. of Materials Science and Metallurgical Engineering; Elvira, C.; San Roman, J. [CSIC, Madrid (Spain). Inst. de Ciencia y Tecnologia de Polimeros

    2001-07-01

    The aim of this work is to study the possibility to improve the mechanical properties of a calcium phosphate cement by adding a polymeric acrylic system supporting a derivative of the aminosalicylic acid. It is shown that besides the analgesic and antiinflammatory properties, the salicylic group present a calcium complexation ability. This feature makes it reasonable to envisage a good bonding between the inorganic and the polymeric phase, which can act as a reinforcing component in the cement. The inorganic phase of the cement studied consisted in {alpha}- tricalcium phosphate ({alpha}-Ca{sub 3}(PO{sub 4}){sub 2}) and precipitated hydroxyapatite as a seed, and the liquid phase was an aqueous solution of Na{sub 2}HPO{sub 4}. The polymeric drug used (poly (4-HMA), where 4-HMA is a methacrylamide derived from 4-aminosalicylic acid) was added in a 5 wt% to the liquid phase. The hydrolysis of the {alpha}-TCP into hydroxyapatite was not prevented, but the polymer produced a delay in the reaction. As a consequence the cement hardening was slightly slower, although the final compressive strength was 25% higher. The bending strength increased noticeably, from 5 MPa to 9 MPa with the addition of the polymeric drug. The strengthening of the structure could be related by SEM observations with the formation of a polymeric network between the entangled crystals of hydroxyapatite. (orig.)

  17. Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel-Drug Binding Kinetics and Multichannel Pharmacology.

    Science.gov (United States)

    Li, Zhihua; Dutta, Sara; Sheng, Jiansong; Tran, Phu N; Wu, Wendy; Chang, Kelly; Mdluli, Thembi; Strauss, David G; Colatsky, Thomas

    2017-02-01

    The current proarrhythmia safety testing paradigm, although highly efficient in preventing new torsadogenic drugs from entering the market, has important limitations that can restrict the development and use of valuable new therapeutics. The CiPA (Comprehensive in vitro Proarrhythmia Assay) proposes to overcome these limitations by evaluating drug effects on multiple cardiac ion channels in vitro and using these data in a predictive in silico model of the adult human ventricular myocyte. A set of drugs with known clinical torsade de pointes risk was selected to develop and calibrate the in silico model. Manual patch-clamp data assessing drug effects on expressed cardiac ion channels were integrated into the O'Hara-Rudy myocyte model modified to include dynamic drug-hERG channel (human Ether-à-go-go-Related Gene) interactions. Together with multichannel pharmacology data, this model predicts that compounds with high torsadogenic risk are more likely to be trapped within the hERG channel and show stronger reverse use dependency of action potential prolongation. Furthermore, drug-induced changes in the amount of electronic charge carried by the late sodium and L-type calcium currents was evaluated as a potential metric for assigning torsadogenic risk. Modeling dynamic drug-hERG channel interactions and multi-ion channel pharmacology improves the prediction of torsadogenic risk. With further development, these methods have the potential to improve the regulatory assessment of drug safety models under the CiPA paradigm. © 2017 American Heart Association, Inc.

  18. A Systems-Pharmacology Analysis of Herbal Medicines Used in Health Improvement Treatment: Predicting Potential New Drugs and Targets

    Directory of Open Access Journals (Sweden)

    Jianling Liu

    2013-01-01

    Full Text Available For thousands of years, tonic herbs have been successfully used all around the world to improve health, energy, and vitality. However, their underlying mechanisms of action in molecular/systems levels are still a mystery. In this work, two sets of tonic herbs, so called Qi-enriching herbs (QEH and Blood-tonifying herbs (BTH in TCM, were selected to elucidate why they can restore proper balance and harmony inside body, organ and energy system. Firstly, a pattern recognition model based on artificial neural network and discriminant analysis for assessing the molecular difference between QEH and BTH was developed. It is indicated that QEH compounds have high lipophilicity while BTH compounds possess high chemical reactivity. Secondly, a systematic investigation integrating ADME (absorption, distribution, metabolism, and excretion prediction, target fishing and network analysis was performed and validated on these herbs to obtain the compound-target associations for reconstructing the biologically-meaningful networks. The results suggest QEH enhance physical strength, immune system and normal well-being, acting as adjuvant therapy for chronic disorders while BTH stimulate hematopoiesis function in body. As an emerging approach, the systems pharmacology model might facilitate to understand the mechanisms of action of the tonic herbs, which brings about new development for complementary and alternative medicine.

  19. Development and Evaluation of an Improved Methodology for Assessing Adherence to Evidence-Based Drug Therapy Guidelines Using Claims Data

    Science.gov (United States)

    Kawamoto, Kensaku; Allen LaPointe, Nancy M.; Silvey, Garry M.; Anstrom, Kevin J.; Eisenstein, Eric L.; Lobach, David F.

    2007-01-01

    Non-adherence to evidence-based pharmacotherapy is associated with increased morbidity and mortality. Claims data can be used to detect and intervene on such non-adherence, but existing claims-based approaches for measuring adherence to pharmacotherapy guidelines have significant limitations. In this manuscript, we describe a methodology for assessing adherence to pharmacotherapy guidelines that overcomes many of these limitations. To develop this methodology, we first reviewed the literature to identify prior work on potential strategies for overcoming these limitations. We then assembled a team of relevant domain experts to iteratively develop an improved methodology. This development process was informed by the use of the proposed methodology to assess adherence levels for 14 pharmacotherapy guidelines related to seven common diseases among approximately 36,000 Medicaid beneficiaries. Finally, we evaluated the ability of the methodology to overcome the targeted limitations. Based on this evaluation, we conclude that the proposed methodology overcomes many of the limitations associated with existing approaches. PMID:18693865

  20. CGP 41251, a new potential anticancer drug, improves contractility of rat isolated cardiac muscle subjected to hypoxia.

    Science.gov (United States)

    Kocic, I; Dworakowska, D; Dworakowski, R; Petrusewicz, J

    2001-06-01

    The aim of the present work was to examine the effects of 4'-N-benzoyl staurosporine (CGP 41251), a protein kinase C inhibitor with broad antiproliferative activity in many cell lines, on the rat isolated heart contractility under normoxic and hypoxic conditions. Additionally, we examined the effects of CGP 41251, WB-4101 (alpha1a -adrenoceptor antagonist), chloroethylclonidine (CEC) (alpha1b-adrenoceptor antagonist) and selective damage of endocardial endothelium by Triton X-100 on the protection against hypoxia induced by preconditioning of rat heart tissue. Experiments were performed on rat isolated left ventricular papillary muscle. The following parameters were measured: force of contraction (Fc), velocity of contraction (+dF/dt) and velocity of relaxation (-dF/dt). The temperature of the bath solution was 37 degrees C +/- 0.5 degrees C, and rate of electrical stimulation was 0.5 Hz. At concentrations less than 1 microM CGP 41251 did not cause any changes in contractility of rat heart. At 1 and 3 microM, significant positive inotropic action was observed. Treatment of rat papillary muscle by CGP 41251 at 3 microM reduced decreasing of contractility by simulated hypoxia and reperfusion. Moreover, protective effects of preconditioning was not affected by addition of CGP 41251 neither at 1 nor at 3 microM. Pretreatment with CEC at 3 microM, and selective damage of endocardial endothelium induced by fast (1-s) immersion of papillary muscle in 0.5% Triton X-100, but not pretreatment with WB-4101, abolished the protective effects of preconditioning. The results imply that CGP 41251 improves contractility of heart muscle under normoxic and hypoxic conditions, and does not alter hypoxic preconditioning in rat isolated cardiac tissue. Moreover, it was shown that alpha1b-adrenoceptors and endocardial endothelium are involved in triggering of preconditioning in rat isolated heart muscle.

  1. How to improve drug dosing for patients with renal impairment in primary care - a cluster-randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Erler Antje

    2012-09-01

    Full Text Available Abstract Background Patients with chronic kidney disease (CKD are at increased risk for inappropriate or potentially harmful prescribing. The aim of this study was to examine whether a multifaceted intervention including the use of a software programme for the estimation of creatinine clearance and recommendation of individual dosage requirements may improve correct dosage adjustment of relevant medications for patients with CKD in primary care. Methods A cluster-randomized controlled trial was conducted between January and December 2007 in small primary care practices in Germany. Practices were randomly allocated to intervention or control groups. In each practice, we included patients with known CKD and elderly patients (≥70 years suffering from hypertension. The practices in the intervention group received interactive training and were provided a software programme to assist with individual dose adjustment. The control group performed usual care. Data were collected at baseline and at 6 months. The outcome measures, analyzed across individual patients, included prescriptions exceeding recommended maximum daily doses, with the primary outcome being prescriptions exceeding recommended standard daily doses by more than 30%. Results Data from 44 general practitioners and 404 patients are included. The intervention was effective in reducing prescriptions exceeding the maximum daily dose per patients, with a trend in reducing prescriptions exceeding the standard daily dose by more than 30%. Conclusions A multifaceted intervention including the use of a software program effectively reduced inappropriately high doses of renally excreted medications in patients with CKD in the setting of small primary care practices. Trial registration Current Controlled Trials ISRCTN02900734

  2. Drug Facts

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    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use Hurts Other People Drug Use Hurts Families Drug Use Hurts Kids Drug Use Hurts Unborn ...

  3. Drug Facts

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    Full Text Available ... Use Hurts Unborn Children Drug Use Hurts Your Health Drug Use Hurts Bodies Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  4. Drug Allergy

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    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  5. Drug Facts

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    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use Hurts Other People Drug Use Hurts Families Drug Use Hurts Kids Drug Use Hurts Unborn ...

  6. Drug Facts

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    Full Text Available ... The Link Between Drug Use and HIV/AIDS Recovery & Treatment Drug Treatment Facts Does Drug Treatment Work? ... and Family Can Help Find Treatment/Rehab Resources Prevent Drug Use Help Children and Teens Stay Drug- ...

  7. A triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor (DSM421) with improved drug-like properties for treatment and prevention of malaria

    Science.gov (United States)

    Phillips, Margaret A.; White, Karen L.; Kokkonda, Sreekanth; Deng, Xiaoyi; White, John; Mazouni, Farah El; Marsh, Kennan; Tomchick, Diana R.; Manjalanagara, Krishne; Rudra, Kakali Rani; Wirjanata, Grennady; Noviyanti, Rintis; Price, Ric N; Marfurt, Jutta; Shackleford, David M.; Chiu, Francis C.K.; Campbell, Michael; Jimenez-Diaz, Maria Belen; Bazaga, Santiago Ferrer; Angulo-Barturen, Iñigo; Martinez, Maria Santos; Lafuente-Monasterio, Maria; Kaminsky, Werner; Silue, Kigbafori; Zeeman, Anne-Marie; Kocken, Clemens; Leroy, Didier; Blasco, Benjamin; Rossignol, Emilie; Rueckle, Thomas; Matthews, Dave; Burrows, Jeremy N.; Waterson, David; Palmer, Michael J.; Rathod, Pradipsinh K.; Charman, Susan A.

    2016-01-01

    The emergence of drug resistant malaria parasites continues to hamper efforts to control this lethal disease. Dihydroorotate dehydrogenase has recently been validated as a new target for the treatment of malaria and a selective inhibitor (DSM265) of the Plasmodium enzyme is currently in clinical development. With the goal of identifying a backup compound to DSM265, we explored replacement of the SF5-aniline moiety of DSM265 with a series of CF3-pyridinyls, while maintaining the core triazolopyrimidine scaffold. This effort led to the identification of DSM421, which has improved solubility, lower intrinsic clearance and increased plasma exposure after oral dosing compared to DSM265, while maintaining a long predicted human half-life. Its improved physical and chemical properties will allow it to be formulated more readily than DSM265. DSM421 showed excellent efficacy in the SCID mouse model of P. falciparum malaria that supports the prediction of a low human dose (<200 mg). Importantly DSM421 showed equal activity against both P. falciparum and P. vivax field isolates, while DSM265 was more active on P. falciparum. DSM421 has the potential to be developed as a single dose cure or once-weekly chemopreventative for both P. falciparum and P. vivax malaria leading to its advancement as a preclinical development candidate. PMID:27641613

  8. Critical analysis of India's National Mission on Medicinal Plants (NMMP in providing access to quality botanical drugs to improve public health

    Directory of Open Access Journals (Sweden)

    Rahi Jain

    2015-01-01

    Full Text Available Drugs play an important role in improving health of the population. Medicinal plants help in addressing the health issues of a large section of the population – especially the low and middle-income people. However, there are some concerns about the supply, efficacy and safety in using them. This study reviews India's major initiative toward medicinal plants namely, the National Mission on Medicinal Plants to meet medicinal plants challenges. The study analyzed the mission's probable shortcomings due to its design and operational details. This study used “content analysis” approach for analysis of mission's publicly available documents, viz. “Operational guidelines” and its two amendments. The study identified prevalent 28 shortcomings in the original document related to clarity of the document; accountability, transparency and stakeholders' representation. These challenges were partially addressed in two amendments, which indicate persistence of shortcomings in design and operational details. The mission can help in improving and strengthening the Ayurveda, Yoga, Unani, Siddha and Homeopathy program by addressing those shortcomings.

  9. Improvement in laboratory diagnosis of wound botulism and tetanus among injecting illicit-drug users by use of real-time PCR assays for neurotoxin gene fragments.

    Science.gov (United States)

    Akbulut, D; Grant, K A; McLauchlin, J

    2005-09-01

    An upsurge in wound infections due to Clostridium botulinum and Clostridium tetani among users of illegal injected drugs (IDUs) occurred in the United Kingdom during 2003 and 2004. A real-time PCR assay was developed to detect a fragment of the neurotoxin gene of C. tetani (TeNT) and was used in conjunction with previously described assays for C. botulinum neurotoxin types A, B, and E (BoNTA, -B, and -E). The assays were sensitive, specific, rapid to perform, and applicable to investigating infections among IDUs using DNA extracted directly from wound tissue, as well as bacteria growing among mixed microflora in enrichment cultures and in pure culture on solid media. A combination of bioassay and PCR test results confirmed the clinical diagnosis in 10 of 25 cases of suspected botulism and two of five suspected cases of tetanus among IDUs. The PCR assays were in almost complete agreement with the conventional bioassays when considering results from different samples collected from the same patient. The replacement of bioassays by real-time PCR for the isolation and identification of both C. botulinum and C. tetani demonstrates a sensitivity and specificity similar to those of conventional approaches. However, the real-time PCR assays substantially improves the diagnostic process in terms of the speed of results and by the replacement of experimental animals. Recommendations are given for an improved strategy for the laboratory investigation of suspected wound botulism and tetanus among IDUs.

  10. Desensitization of B-adrenergic receptors following repeated injections of 2-substituted-4-phenylquinolines

    Energy Technology Data Exchange (ETDEWEB)

    Alhaider, A.A.

    1986-03-05

    In a previous work, they synthesized some new 2-substituted-4-phenylquinoline derivatives which demonstrated potent antidepressant activities as revealed by their antagonism to the uptake of /sup 3/(H)-norepinephrine and /sup 3/(H)-serotonin into brain synaptosomal preparation. Also, these compounds have demonstrated less anticholinergic, antihistamine and cardiovascular effects as compared to imipramine in animal models. In this present work, the chronic effects of some of these compounds on the sensitivity of the noradrenergic cyclic-AMP generating system on rat brain cortex has been conducted by the daily injection of 20 mg/kg i.p. for a period of three weeks. Imipramine and trazodone were utilized as standards, representing typical and atypical antidepressants, respectively. Acute treatment (single dose 20 mg/kg) and subchronic treatment (20 mg/kg for 10 days) produced no significant desensitization of the B-adrenoceptors. However, chronic treatment with the compounds significantly decreased isoprenaline-induced increase in c-AMP in the cortex which suggests desensitization of B-adrenoceptors. This effect coupled with the previous findings point to a potential rule of these compounds as suitable antidepressant candidates.

  11. A strategy to improve the detection of drug-induced hepatotoxicity Una estrategia para mejorar la detección de hepatotoxicidad por medicamentos

    Directory of Open Access Journals (Sweden)

    A. Ruiz Montero

    2005-03-01

    Full Text Available Aims: to report a new strategy for the detection of hepatotoxic adverse drug reactions (ADRs in hospitalized patients improving the results obtained with other methods. Design: the model is based on the identification of a single alert signal in various target clinical departments over a 12-month period. Each patient was later interviewed following a set protocol. The main results analyzed were the drugs suspected of ADR; causal relationship between suspected drugs and ADRs; ADR severity, and incidence of hepatotoxic ADR/100,000 inhabitants. Subjects: population served by a university-affiliated urban teaching hospital (519,381 inhabitants. Results: The overall ratio of confirmed/suspected ADRs was high (35/80. The most commonly reported drug was amoxicillin-clavulanic acid (4 cases. With regard to causality, 2 suspected cases were classified as definite and 14 as probable. The distribution according to the severity of hepatotoxicity was 6 severe and 29 mild cases. The incidence of hepatotoxic ADRs/100,000 inhabitants as revealed by our method was much higher versus voluntary report (6.74 and 1.79, respectively. Conclusions: our method has proven effective for improving the detection of hepatotoxic ADRs, and may be extended to other types of adverse reactions.Objetivos: comunicar una nueva estrategia para la detección de reacciones hepatotóxicas por medicamentos que mejora los resultados obtenidos con otros métodos utilizados. Diseño: el modelo se basa en la identificación de una señal de alerta simple en los pacientes de varios servicios diana, durante 12 meses. Cada paciente fue posteriormente entrevistado siguiendo un protocolo específico. Se analizaron: los fármacos sospechosos de producir hepatotoxicidad, la relación de causalidad entre el fármaco sospechoso y la hepatotoxicidad, la gravedad y la incidencia de hepatotoxicidad medicamentosa/100.000 habitantes. Pacientes: la población del área de influencia de nuestro hospital

  12. Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice.

    Science.gov (United States)

    Moriguchi, Shigeki; Tanaka, Tomoya; Tagashira, Hideaki; Narahashi, Toshio; Fukunaga, Kohji

    2013-04-01

    Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKIIα (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKCα (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR.

  13. Drugs and Drug Abuse.

    Science.gov (United States)

    Anastas, Robert, Comp.; And Others.

    GRADES OR AGES: Secondary grades. SUBJECT MATTER: Drugs and drug abuse. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into several sections, each of which is in outline or list form. It is xeroxed and spiral-bound with a paper cover. OBJECTIVES AND ACTIVITIES: No objectives are mentioned. The major portion of the guide contains a…

  14. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  15. Mucoactive drugs

    Directory of Open Access Journals (Sweden)

    R. Balsamo

    2010-06-01

    Full Text Available Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal infection and/or inflammation associated with these diseases often gives rise to inflammatory products, including neutrophil-derived DNA and filamentous actin, in addition to bacteria, apoptotic cells and cellular debris, that may collectively increase mucus production and viscosity. Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical complication. The main purpose of mucoactive drugs is to increase the ability to expectorate sputum and/or decrease mucus hypersecretion. Many mucoactive drugs are currently available and can be classified according to their putative mechanism of action. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics. By developing our understanding of the specific effects of mucoactive agents, we may result in improved therapeutic use of these drugs. The present review provides a summary of the most clinically relevant mucoactive drugs in addition to their potential mechanism of action.

  16. A case study using a patient satisfaction survey to improve the delivery and effectiveness of drug addiction treatment services: marketing implications and organizational impact.

    Science.gov (United States)

    Hogan, Beth; Hershey, Lewis; Ritchey, Steven

    2007-01-01

    Drug abuse and addiction continues to negatively impact many lives in this country. The United States health care system has grappled with how to best serve this vulnerable population. Since the personal and societal costs of addiction are high, all recent iterations of the United States strategic health plans (such as Healthy People 2010) have prioritized this area for improvement. At the local level, health care providers who care for those with addictions are challenged with shrinking insurance coverage for services, a difficult patient population, lack of treatment options, growing ranks of indigent patients, as well as a plethora of additional management challenges. It is known that successful treatment is integrally linked with patient satisfaction with services. The most critical factors in successful addiction treatment (from a patient's perspective) are (1) their belief that the counselor cares about them and, (2) their belief that they can recover. This paper reports a case study in the use of a patient satisfaction survey as a quality management/service refinement tool within a methadone treatment setting. Results indicate that the use of the survey itself provides patients with a tangible cue supporting the presence of the critical success factors. Further, the use of a survey provides a baseline for future measurements and trending. The paper concludes with a discussion of the marketing and organizational implications of incorporating the patient satisfaction survey into the ongoing delivery program for addiction services.

  17. KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability

    Directory of Open Access Journals (Sweden)

    Kevin Farmer

    2012-01-01

    Full Text Available KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.

  18. KU-32, a novel drug for diabetic neuropathy, is safe for human islets and improves in vitro insulin secretion and viability.

    Science.gov (United States)

    Farmer, Kevin; Williams, S Janette; Novikova, Lesya; Ramachandran, Karthik; Rawal, Sonia; Blagg, Brian S J; Dobrowsky, Rick; Stehno-Bittel, Lisa

    2012-01-01

    KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.

  19. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  20. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  1. Drug Facts

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    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? Do You or a Loved One Have a Drug Use Problem? Signs of Drug Use and Addiction How Does Drug Use Become Addiction? Addiction Risk ...

  2. Drug Facts

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    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  3. 提高药学专业药物合成技能的实验教学探索%Improvement of Improving the Skills of Medicine Drug Synthesis Experiments Teaching

    Institute of Scientific and Technical Information of China (English)

    谢集照; 徐佳佳; 赵农

    2014-01-01

    In order to improve the drug synthesis skill for students majored in medicine , organic chemistry and pharmaceutical chemistry experiment were integrated.Experiment content and teaching methods were optimized that three-step program was put forward , in stages to solve basic unit operations , comprehensive experiment and the ability to retrieve literature , to solve practical problems , and innovation ability.At the same time , the evaluation system was improved, the first two stages of assessment paying equal attention to theory and operation of examination , the basic knowledge and the integrated use of paying equal attention to , and the third stage of assessment from the traditional pure individual scoring into teams and individuals jointly score.%为提高药学专业学生的药物合成技能,我们整合有机化学和药物化学实验,优化实验内容和教学方法:提出三段式培养计划,分阶段解决培养基本单元操作、综合实验和检索文献能力、解决实际问题和创新能力。同时改进考核评价体系:前两个阶段的考核,理论考核与操作考核并重,基础知识和综合运用并重;第三阶段的考核,从传统的单纯个人得分变成团队和个人共同得分。

  4. 生活方式与非药物调脂%A lifestyle and a non-drug therapy for improving blood lipid

    Institute of Scientific and Technical Information of China (English)

    李论; 李贵学

    2015-01-01

    目的::通过养成饮用牛奶并坚持有氧运动的生活方式,探讨非药物调脂的途径。方法:体检的32名血脂异常者(排除后),并将其血脂数据作为首次检测数据。采取早餐饮用纯牛奶,3个月后复查血脂;继续饮用该奶品,同时坚持有氧运动3个月,再行血脂检测,将以上两组数据分别与首次检测数据进行对比分析。结果:第二次检测数据与原始数据之间差异仅部分有统计学意义(P<0.05),第三次检测数据与原始数据间差异大部分有统计学意义(P<0.05)。结论:通过本项研究,初步认为单纯饮用牛奶,调脂作用有限,坚持饮用牛奶并配合有氧运动,调脂作用明显,多种健康生活方式对血脂的改善可能具有协同效应。%Objective:To explore a lifestyle and a non-drug therapy ( drinking milk and aerobic exercise) in improvement of blood lipid. Methods:All 32 subjects who were inadvertent dyslipidemia in a health examination were randomly selected. The raw da-ta of blood lipid is recorded. They drank pure milk for breakfast every morning for 3 month and their blood lipids were tested;then they continued to drank the pure milk, and did aerobic exercise at the same time for 3 months, and their blood lipids were retested. The re-sulting data were analyzed and compared with the original data. Results: The difference from partial data was statistically significant (P<0. 05) between the first and second examination. The difference from most data was statistically significant (P<0. 05) between the first and third examination. Conclusions:Drinking milk can partially improve composition of blood lipid . As a lifestyle , long-term consumption of milk with aerobic exercise can improve the composition obviously. A variety of beneficial factors may have a synergistic effect .

  5. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA

    DEFF Research Database (Denmark)

    Douthwaite, S; Hansen, L H; Mauvais, P

    2000-01-01

    to A752 via alkyl-aryl groups linked to a carbamate at the drug 11/12 position (in the ketolide antibiotics HMR 3647 and HMR 3004). The data indicate that simultaneous drug interactions with domains II and V strengthen binding and that the domain II contact is of particular importance to achieve...

  6. Educational intervention to improve physician reporting of adverse drug reactions (ADRs in a primary care setting in complementary and alternative medicine

    Directory of Open Access Journals (Sweden)

    Ostermann Thomas

    2009-07-01

    Full Text Available Abstract Background Recent studies have shown that adverse drug reactions (ADRs are underreported. This may be particularly true of ADRs associated with complementary and alternative medicine (CAM. Data on CAM-related ADRs, however, are sparse. Objective was to evaluate the impact of an educational intervention and monitoring programme designed to improve physician reporting of ADRs in a primary care setting. Methods A prospective multicentre study with 38 primary care practitioners specialized in CAM was conducted from January 2004 through June 2007. After 21 month all physicians received an educational intervention in terms of face-to-face training to assist them in classifying and reporting ADRs. The study centre monitored the quantity and quality of ADR reports and analysed the results. To measure changes in the ADR reporting rate, the median number of ADR reports and interquartile range (IQR were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Interrater reliability between the physicians and the study centre was calculated using Cohen's kappa with a 95% confidence interval (CI. We used Mann Whitney U-test for testing continuous data and chi-square test was used for categorical data. The level of statistical significance was set at P Results A total of 404 ADRs were reported during the complete study period. An initial 148% increase (P = 0.001 in the number of ADR reports was observed after the educational intervention. Compared to baseline the postinterventional number of ADR reportings was statistically significant higher (P P Conclusion The results of the present study demonstrate that an educational intervention can increase physician awareness of ADRs. Participating physicians were able to incorporate the knowledge they had gained from face-to-face training into their

  7. Educational intervention to improve physician reporting of adverse drug reactions (ADRs) in a primary care setting in complementary and alternative medicine.

    Science.gov (United States)

    Tabali, Manuela; Jeschke, Elke; Bockelbrink, Angelina; Witt, Claudia M; Willich, Stefan N; Ostermann, Thomas; Matthes, Harald

    2009-07-31

    Recent studies have shown that adverse drug reactions (ADRs) are underreported. This may be particularly true of ADRs associated with complementary and alternative medicine (CAM). Data on CAM-related ADRs, however, are sparse.Objective was to evaluate the impact of an educational intervention and monitoring programme designed to improve physician reporting of ADRs in a primary care setting. A prospective multicentre study with 38 primary care practitioners specialized in CAM was conducted from January 2004 through June 2007. After 21 month all physicians received an educational intervention in terms of face-to-face training to assist them in classifying and reporting ADRs. The study centre monitored the quantity and quality of ADR reports and analysed the results.To measure changes in the ADR reporting rate, the median number of ADR reports and interquartile range (IQR) were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Interrater reliability between the physicians and the study centre was calculated using Cohen's kappa with a 95% confidence interval (CI). We used Mann Whitney U-test for testing continuous data and chi-square test was used for categorical data. The level of statistical significance was set at P educational intervention. Compared to baseline the postinterventional number of ADR reportings was statistically significant higher (P educational intervention. The quality of ADR reports increased from kappa 0.15 (95% CI: 0.08; 0.29) before to 0.43 (95% CI: 0.23; 0.63) after the intervention. The results of the present study demonstrate that an educational intervention can increase physician awareness of ADRs. Participating physicians were able to incorporate the knowledge they had gained from face-to-face training into their daily clinical practice. However, the effects of the intervention

  8. Blood pressure reductions following catheter-based renal denervation are not related to improvements in adherence to antihypertensive drugs measured by urine/plasma toxicological analysis.

    Science.gov (United States)

    Ewen, Sebastian; Meyer, Markus R; Cremers, Bodo; Laufs, Ulrich; Helfer, Andreas G; Linz, Dominik; Kindermann, Ingrid; Ukena, Christian; Burnier, Michel; Wagenpfeil, Stefan; Maurer, Hans H; Böhm, Michael; Mahfoud, Felix

    2015-12-01

    Renal denervation can reduce blood pressure in patients with uncontrolled hypertension. The adherence to prescribed antihypertensive medication following renal denervation is unknown. This study investigated adherence to prescribed antihypertensive treatment by liquid chromatography-high resolution tandem mass spectrometry in plasma and urine at baseline and 6 months after renal denervation in 100 patients with resistant hypertension, defined as baseline office systolic blood pressure ≥140 mmHg despite treatment with ≥3 antihypertensive agents. At baseline, complete adherence to all prescribed antihypertensive agents was observed in 52 patients, 46 patients were partially adherent, and two patients were completely non-adherent. Baseline office blood pressure was 167/88 ± 19/16 mmHg with a corresponding 24-h blood pressure of 154/86 ± 15/13 mmHg. Renal denervation significantly reduced office and ambulatory blood pressure at 6-month follow-up by 15/5 mmHg (p treatment was significantly reduced from 85.0 % at baseline to 80.7 %, 6 months after renal denervation (p = 0.005). The blood pressure decrease was not explained by improvements in adherence following the procedure. Patients not responding to treatment significantly reduced their drug intake following the procedure. Adherence was highest for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta blockers (>90 %) and lowest for vasodilators (21 %). In conclusion, renal denervation can reduce office and ambulatory blood pressure in patients with resistant hypertension despite a significant reduction in adherence to antihypertensive treatment after 6 months.

  9. Evaluation of an Improved U.S. Food and Drug Administration Method for the Detection of Cyclospora cayetanensis in Produce Using Real-Time PCR.

    Science.gov (United States)

    Murphy, Helen R; Lee, Seulgi; da Silva, Alexandre J

    2017-07-01

    Cyclospora cayetanensis is a protozoan parasite that causes human diarrheal disease associated with the consumption of fresh produce or water contaminated with C. cayetanensis oocysts. In the United States, foodborne outbreaks of cyclosporiasis have been linked to various types of imported fresh produce, including cilantro and raspberries. An improved method was developed for identification of C. cayetanensis in produce at the U.S. Food and Drug Administration. The method relies on a 0.1% Alconox produce wash solution for efficient recovery of oocysts, a commercial kit for DNA template preparation, and an optimized TaqMan real-time PCR assay with an internal amplification control for molecular detection of the parasite. A single laboratory validation study was performed to assess the method's performance and compare the optimized TaqMan real-time PCR assay and a reference nested PCR assay by examining 128 samples. The samples consisted of 25 g of cilantro or 50 g of raspberries seeded with 0, 5, 10, or 200 C. cayetanensis oocysts. Detection rates for cilantro seeded with 5 and 10 oocysts were 50.0 and 87.5%, respectively, with the real-time PCR assay and 43.7 and 94.8%, respectively, with the nested PCR assay. Detection rates for raspberries seeded with 5 and 10 oocysts were 25.0 and 75.0%, respectively, with the real-time PCR assay and 18.8 and 68.8%, respectively, with the nested PCR assay. All unseeded samples were negative, and all samples seeded with 200 oocysts were positive. Detection rates using the two PCR methods were statistically similar, but the real-time PCR assay is less laborious and less prone to amplicon contamination and allows monitoring of amplification and analysis of results, making it more attractive to diagnostic testing laboratories. The improved sample preparation steps and the TaqMan real-time PCR assay provide a robust, streamlined, and rapid analytical procedure for surveillance, outbreak response, and regulatory testing of foods for

  10. The development of improved and new in vitro assays for detecting the genotoxic and non-genotoxic carcinogenic potential of chemicals in the discovery phase of drug development

    NARCIS (Netherlands)

    Westerink, W.M.A.

    2011-01-01

    In drug development, toxicity is an important factor for attrition, resulting in a failure rate of 30%-40%. Hepatotoxicity, nephrotoxicity, cardiovascular safety, reproduction toxicity, developmental toxicity (teratogenicity), genotoxicity and carcinogenicity are the main causes for attrition in saf

  11. Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries

    DEFF Research Database (Denmark)

    Hansen, K W; Kaiser, C; Hvelplund, A

    2013-01-01

    To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels.......To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels....

  12. Drug Facts

    Medline Plus

    Full Text Available ... and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of ... to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? Effects of ...

  13. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  14. Drug Resistance

    Science.gov (United States)

    HIV Treatment Drug Resistance (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  15. DRUG POISONING IN SLOVENIA

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2008-01-01

    Poisoning by drugs for the nervous system, particularly benzodiazepines, is the most commonform of poisoning by drugs in Slovenia. It would be necessary to report all acutelypoisoned patients to the Register of Intoxications, since we need data about all poisoningin Slovenia to improve their prophylaxis and treatment

  16. Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates

    Directory of Open Access Journals (Sweden)

    Gao Y

    2015-02-01

    Full Text Available Ya Gao,1,* Ya-zhuo Hu,1,* Rui-sheng Li,2 Zhi-tao Han,1 Yan Geng,1 Zheng Xia,1 Wen-jin Du,3 Li-xin Liu,4 Hong-hong Zhang,1 Lu-ning Wang5 1Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, 2Research and Technology Service Center, PLA 302 Hospital, 3Department of Neurology, Air Force General Hospital, 4Department of Neurology, Beijing Geriatric Hospital, 5Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work and are joint first authors Background: Cattle encephalon glycoside and ignotin injection (CEGI, a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People’s Republic of China. However, data regarding the effect of CEGI on Alzheimer’s disease (AD remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1+ activated microglia

  17. Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network

    Science.gov (United States)

    Rowan, Christopher G.; Brunelli, Steven M.; Munson, Jeffrey; Flory, James; Reese, Peter P.; Hennessy, Sean; Lewis, James; Mines, Daniel; Barrett, Jeffrey S.; Bilker, Warren; Strom, Brian L.

    2014-01-01

    Objective To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme. Background Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism. Methods Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score. Results The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362 809 patients and 792 665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90–1.66). There were 1449 renal dysfunction events among 272,099 patients and 574 584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58–1.44). There were 1434 hepatic dysfunction events among 367 612 patients and 815 945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45–1.31). Conclusions Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4

  18. Which Form of Medical Training is the Best in Improving Interns’ knowledge Related to Advanced Cardiac Life Support Drugs Pharmacology? An Educational Analytical Intervention Study Between Electronic Learning and Lecture-Based Education

    Science.gov (United States)

    Khoshbaten, Manouchehr; Soleimanpour, Hassan; Ala, Alireza; Shams Vahdati, Samad; Ebrahimian, Kimia; Safari, Saeid; Golzari, Samad EJ; Salek Ranjbarzadeh, Fariba; Mehdizadeh Esfanjani, Robab

    2014-01-01

    Background: Conventional educational systems seem to be improper throughout the cardiopulmonary resuscitation (CPR) teaching process. The most common causes of failed resuscitation are unfamiliarity with cardiopulmonary resuscitation algorithms, poor performance of leader of the CPR team and lack of skilled personnel, coordination among members during resuscitation, and responsibility of staff. Objectives: Electronic learning, as a new educational method is controversial issue in medical education for improving physicians’ practical knowledge and it is inevitable that further research on its effectiveness should be done. Materials and Methods: The present study is a prospective, pre- and post-educational, cross-sectional research, in which 84 interns were randomly divided into two groups. pre- and post- educational interventions that took place in the Department of Emergency Medicine, interns were evaluated by 21 multiple choice questions related to American Heart Association guidelineson cardiopulmonary resuscitation drugs. Questions were assessed in terms of routes for CPR drugs administration, CPR drug dosage forms, clinical judgment and appropriate CPR drug administration, and the alternative drugs in emergency situations. Data were analyzed by generalized estimating equations regression models and P < 0.05 was considered statistically significant. Results: Evaluating the effectiveness of both educational methods revealed that the mean answering score for 21 questions before education was 7.5 ± 2.6 and no significant difference was observed in groups (P = 0.55). However, after education, the average scores significantly increased to 11.0 ± 3.9 (P < 0.001). Electronic learning method was not associated with considerable increase in the knowledge of interns in this group compared with the lecture-based group (P = 0.49). Conclusions: No significant differences were observed between electronic learning and lecture-based education in improving interns

  19. Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in bresat cancer cells: an improved nanomedicine strategies

    Science.gov (United States)

    Murugan, Chandran; Rayappan, Kathirvel; Thangam, Ramar; Bhanumathi, Ramasamy; Shanthi, Krishnamurthy; Vivek, Raju; Thirumurugan, Ramasamy; Bhattacharyya, Atanu; Sivasubramanian, Srinivasan; Gunasekaran, Palani; Kannan, Soundarapandian

    2016-01-01

    Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade of CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium. PMID:27725731

  20. Metallomics in drug development

    DEFF Research Database (Denmark)

    Nguyen, Trinh Thi Nhu Tam; Ostergaard, Jesper; Stürup, Stefan;

    2013-01-01

    A capillary electrophoresis inductively coupled plasma mass spectrometry method for separation of free cisplatin from liposome-encapsulated cisplatin and protein-bound cisplatin was developed. A liposomal formulation of cisplatin based on PEGylated liposomes was used as model drug formulation...... to plasma constituents in plasma samples. It was demonstrated that this approach is suitable for studies of the stability of liposome formulations as leakage of active drug from the liposomes and subsequent binding to biomolecules in plasma can be monitored. This methodology has not been reported before...... and will improve characterization of liposomal drugs during drug development and in studies on kinetics....

  1. Evaluating the efficacy of memantine on improving cognitive functions in epileptic patients receiving anti-epileptic drugs: A double-blind placebo-controlled clinical trial (Phase IIIb pilot study)

    OpenAIRE

    Priya Marimuthu; Sathyanarayanan Varadarajan; Muthuraj Krishnan; Sundar Shanmugam; Gireesh Kunjuraman; Jamuna Rani Ravinder; Balasubramanian Arumugam; Divya Alex; Porchelvan Swaminathan

    2016-01-01

    Objectives: People with epilepsy have greater cognitive and behavioral dysfunction than the general population. There is no specific treatment available for cognitive impairment of these patients. We aimed to evaluate the effects of memantine, an N-methyl-D-aspartate-type glutamate receptor noncompetitive antagonist, on improving cognition and memory functions in epileptic patients with cognitive and memory impairment, who received anti-epileptic drugs (AEDs). Methods: We did a randomized, do...

  2. Layer-by-Layer Coating of Solid Drug Cores: A Versatile Method to Improve Stability, Control Release and Tune Surface Properties.

    Science.gov (United States)

    Polomska, Anna; Leroux, Jean-Christophe; Brambilla, Davide

    2017-01-01

    Layer-by-layer coating is a simple and versatile technique based on the sequential deposition of molecular species on planar surfaces or colloidal templates. Its relevance in drug delivery primarily emerges from its versatility to control the release rate of the cargo encapsulated within the colloidal core. The focus of this review is the layer-by-layer encapsulation of colloidal particles purely composed of drug, including the core fabrication step, coating materials and techniques, multilayer shell permeability control, and reported in vitro and in vivo outcomes.

  3. 品管圈对提高多重耐药菌管理总结分析率的效果%Effect of Quality Control Circle on Improving the Management of Multi Drug Resistant Bacteria

    Institute of Scientific and Technical Information of China (English)

    曹兰芳; 刘萍; 石晓院; 余彩娥; 邹楠茜

    2015-01-01

    Objective Analysis of the establishment ofmultidrugresistantbacteriabeforeandafter the Departmentofqualitycontrol cir-cleof multi drug resistant strainsofchange management。Methods During the period of 2-10 months of 2014,In our hospital by the multi sectoral, multidisciplinary establishment of multi drug resistant bacteria QCC,Department of management of multi drug resis-tant bacteria were analyzed supervision and management,Compared with those in the establishment of QCC before 2014 January,Observation of sections of the multi drug resistant bacteria of change management. Results The QCC activities before and after the Department of management summary of theanalysis of multi drug resistant bacteria increased from 2014 to January rose from 7.6%in 2014 to 92.4% in October. Conclusion Multi sectoral joint QCC activities can improve the cognition of multi drug resistant bacteriain medical staff,To further implement the measures,To improve the management of multiple drug-resistant rate,To ensure the safety of patients,To improve the quality of medical care,It is worth in clinical promotion.%目的:分析成立多重耐药菌品管圈前后科室对多重耐药菌管理总结分析的变化。方法2014年2~10月期间,该院由多部门、多学科组成成立多重耐药菌品管圈,对科室多重耐药菌管理总结分析进行监督管理,与未成立品管圈活动前的2014年1月比较,观察科室对多重耐药菌管理总结分析的变化。结果品管圈活动开展前后科室对多重耐药菌管理总结的分析率由2014年1月的7.6%上升至2014年10月的92.4%。结论多部门联合开展品管圈活动能提高医务人员对多重耐药菌的认知,措施得到进一步落实,提高对多重耐药菌管理总结分析率,保障患者安全,提高医疗质量,值得在临床推广。

  4. [Cost] effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: Design of a multicenter randomized controlled trial (IMPROveFALL-study)

    NARCIS (Netherlands)

    K.A. Hartholt (Klaas); N. van der Velde (Nathalie); E.M.M. van Lieshout (Esther); S. Polinder (Suzanne); O.J. de Vries (Oscar); N.D.A. Boyé (Nicole); A.L.A. Kerver (Anton); G. Ziere; M.M.M. Bruijninckx (Milko); F.U.S. Mattace Raso (Francesco); A.G. Uitterlinden (André); E.F. van Beeck (Ed); P. Lips (Paul); P. Patka (Peter); T.J.M. van der Cammen (Tischa)

    2011-01-01

    textabstractBackground: Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the

  5. Interlaboratory validation of an improved U.S. Food and Drug Administration method for detection of Cyclospora cayetanensis in produce using TaqMan real-time PCR

    Science.gov (United States)

    A collaborative validation study was performed to evaluate the performance of a new U.S. Food and Drug Administration method developed for detection of the protozoan parasite, Cyclospora cayetanensis, on cilantro and raspberries. The method includes a sample preparation step in which oocysts are re...

  6. Using Rich Data on Comorbidities in Case-Control Study Design with Electronic Health Record Data Improves Control of Confounding in the Detection of Adverse Drug Reactions

    Science.gov (United States)

    Chase, Herbert

    2016-01-01

    Recent research has suggested that the case-control study design, unlike the self-controlled study design, performs poorly in controlling confounding in the detection of adverse drug reactions (ADRs) from administrative claims and electronic health record (EHR) data, resulting in biased estimates of the causal effects of drugs on health outcomes of interest (HOI) and inaccurate confidence intervals. Here we show that using rich data on comorbidities and automatic variable selection strategies for selecting confounders can better control confounding within a case-control study design and provide a more solid basis for inference regarding the causal effects of drugs on HOIs. Four HOIs are examined: acute kidney injury, acute liver injury, acute myocardial infarction and gastrointestinal ulcer hospitalization. For each of these HOIs we use a previously published reference set of positive and negative control drugs to evaluate the performance of our methods. Our methods have AUCs that are often substantially higher than the AUCs of a baseline method that only uses demographic characteristics for confounding control. Our methods also give confidence intervals for causal effect parameters that cover the expected no effect value substantially more often than this baseline method. The case-control study design, unlike the self-controlled study design, can be used in the fairly typical setting of EHR databases without longitudinal information on patients. With our variable selection method, these databases can be more effectively used for the detection of ADRs. PMID:27716785

  7. Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Bartelink, Imke H.; Bredius, Robbert G. M.; Ververs, Tessa T.; Raphael, Martine F.; van Kesteren, Charlotte; Bierings, Marc; Rademaker, Carin M. A.; den Hartigh, J.; Uiterwaal, Cuno S. P. M.; Zwaveling, Juliette; Boelens, Jaap J.

    2008-01-01

    Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). Th

  8. Comparison of the Effects of Cooperative Learning and Traditional Learning Methods on the Improvement of Drug-Dose Calculation Skills of Nursing Students Undergoing Internships

    Science.gov (United States)

    Basak, Tulay; Yildiz, Dilek

    2014-01-01

    Objective: The aim of this study was to compare the effectiveness of cooperative learning and traditional learning methods on the development of drug-calculation skills. Design: Final-year nursing students ("n" = 85) undergoing internships during the 2010-2011 academic year at a nursing school constituted the study group of this…

  9. Environmental Management Approach to Improve College Student and Community Relations to Reduce Binge and High-Risk Alcohol Use and Other Drug Problems. Prevention Update

    Science.gov (United States)

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2011

    2011-01-01

    A central feature of the U.S. Department of Education's Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention is the promotion of multiple prevention strategies that affect campus and surrounding community environments as a whole and can, thereby, have a large-scale effect on the entire campus community. In outlining the…

  10. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients

    DEFF Research Database (Denmark)

    Petersen, Susanne G; Beyer, Nina; Hansen, Mette Rud;

    2011-01-01

    To investigate the effect of 12 weeks of strength training in combination with a nonsteroidal anti-inflammatory drug (NSAID), glucosamine, or placebo on muscle cross-sectional area (CSA), strength (primary outcome parameters), and function, power, pain, and satellite cell number (secondary outcome...

  11. Simultaneous separation of antihyperlipidemic drugs by green ultrahigh-performance liquid chromatography–diode array detector method: Improving the health of liquid chromatography

    Directory of Open Access Journals (Sweden)

    Mansoor Alghazi

    2017-04-01

    Full Text Available Statins in combination with fibrates show beneficial effects on the lipoprotein profile of patients because they have positive complimentary effects on lipid profile. A new green ultrahigh-performance liquid chromatography–diode array detector method for simultaneous analysis of simvastatin (SMV and fenofibrate (FNF in standard form, marketed formulations, and self-emulsifying drug delivery system formulations was developed and validated in the present investigation. The method utilized C18 as stationary phase and a combination of methanol:water (8:2 as an eluent. It was found that selected eluent provided short run time (2.5 minutes, better peak symmetry and satisfactory values of other chromatographic parameters such as resolution (Rs=2.325, capacity factor (k, 3.0 and 4.2 for SMV and FNF, respectively, selectivity (α =1.4, and number of theoretical plates (N, 4265 and 5285 for SMV and FNF, respectively. An excellent linear relationship (r2 0.998 and 0.997 for SMV and FNF, respectively was observed for linear regression data for the calibration plots. The developed system was validated for accuracy, precision, robustness (˃ 2% for both drugs and recovery (98–102% for both drugs. Results obtained from the statistical treatment of the values obtained for different parameters proved that the method is suitable, reproducible, and selective for the simultaneous analysis of SMV and FNF in bulk, marketed, and self-emulsifying drug delivery system formulations. The replacement of commonly applied toxic solvents with innocuous and environmentally benign solvents provides a better option than the more toxic processes in drug analysis.

  12. The role of Clinical Pharmacists in the improvement of a pharmacovigilance system: A review of the reported adverse drug reactions during 2004-2010 in Mazandaran Province of Iran

    Directory of Open Access Journals (Sweden)

    Elham Azhdari

    2013-02-01

    Full Text Available Background: Following establishment of Iranian Adverse Drug Reaction (ADR Monitoring Center in 1997, ADR committees were established in all hospitals of Mazandaran Province of Iran. Clinical pharmacists from Mazandaran University of Medical Sciences have been involved with these committees since 2007. The aim of this study was to compare the results of the pharmacovigilance system before and after active involvement of clinical pharmacists. Methods: This study included Yellow Cards filled out by healthcare providers in Mazandaran Province during 2004-2010. Frequency of Adverse Drug Reactions (ADRs, route of administration, reporters, number of reports in each years and damaged organs were focuses. Statistical analysis was performed by SPSS 16 software. P Results: A total of 793 yellow cards were completed during 2004 – 2010. Only 38 ADRs (4.8% were related to 2004-2007. Most of the reports generated by Nurses (49.3% followed by Pharmacists and Physicians (P Conclusion: Clinical pharmacists’ intervention regarding establishing ADR committees in the hospitals improved the output of the pharmacovigilance system, although under-reporting is still a major drawback of spontaneous reporting. Keywords: Pharmacovigilance, Adverse Drug Reaction, Mazandaran, Adverse Drug Reaction Reporting Systems

  13. Hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform: an advanced vehicle for topical delivery of antiglaucoma drugs and a likely solution to improving compliance and adherence in glaucoma management.

    Science.gov (United States)

    Yang, Hu; Leffler, Christopher T

    2013-03-01

    Glaucoma therapy typically begins with topical medications, of which there are 4 major classes in common use in the United States: beta-adrenergic antagonists, alpha-agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Unfortunately, all 4 classes require at least daily dosing, and 3 of the 4 classes are approved to be administered 2 or 3 times daily. This need for frequent dosing with multiple medications makes compliance difficult. Longer-acting formulations and combinations that require less frequent administration might improve compliance and therefore medication effectiveness. Recently, we developed an ocular drug delivery system, a hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform for delivering glaucoma therapeutics topically. This platform is designed to deliver glaucoma drugs to the eye efficiently and release the drug in a slow fashion. Furthermore, this delivery platform is designed to be compatible with many of the glaucoma drugs that are currently approved for use. In this article, we review this new delivery system with in-depth discussion of its structural features, properties, and preclinical application in glaucoma treatment. In addition, future directions and translational efforts for marketing this technology are elaborated.

  14. 品管圈用于提高门诊西药房药品质量管理实践%Application of Quality Control Circle for Improving Drug Quality Management in Outpatient Western Medicine Pharmacy of Our Hospital

    Institute of Scientific and Technical Information of China (English)

    李杨华; 周祖萍

    2015-01-01

    目的:提高门诊西药房药品质量管理水平。方法根据门诊患者满意度调查表,收集患者意见,其中81.2%的不满因药品管理不善导致。采用头脑风暴法分析导致药品质量的原因,为药品潮解、药品失效、冷藏药品没按贮藏条件冷藏。按照品管圈的十大步骤实施各项活动,拟订活动计划、拟订对策及实施,评价有形成果(药品质量管理提高)和无形成果(圈能力),制订标准化工作流程。结果药品潮解主要是因协定处方及拆零片剂所致;药品失效主要是因药师工作责任心不强,积压药品所致;冷藏药品未冷藏保管主要因冷藏药品品种多、数量大、冰柜少所致。针对以上原因,采取协定处方标准化分装,请领药品规范化,冷藏药品采取少量多批领取并增加冷柜的方法,对药师增强工作责任心等系列措施。活动后潮解药品由活动前的13次下降到5次,失效药品由活动前的5次下降到2次,冷藏管理药品由活动前的16次下降到6次;同时圈员们的工作积极性、团队凝聚力、解决问题的能力等方面均有大幅提高。结论品管圈管理模式的应用,可提高医院门诊西药房的药品质量管理水平。%Objective To improve the drug quality management of outpatient western medicine pharmacy. Methods The opinions of pa-tients were collected according to the outpatient satisfaction questionnaire, in which 81. 2% was caused by the drugs mismanage-ment. The brainstorming method was adopted to analyze the causes leading to the drug quality problems, including the drug deliques-cence, drug invalidation and cold storage of refrigerated drugs without according to storage conditions. The various activities were imple-mented according to 10 steps of quality control circle ( QCC ) , the plan, countermeasures and implementation of activities were protocolled, the tangible results ( improvement of drug

  15. Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits.

    Science.gov (United States)

    Wunberg, Tobias; Hendrix, Martin; Hillisch, Alexander; Lobell, Mario; Meier, Heinrich; Schmeck, Carsten; Wild, Hanno; Hinzen, Berthold

    2006-02-01

    Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME-Tox) profiling is needed to help identify hits with a minimum number of (known) liabilities. This is particularly true for drug-like hits. Herein, we describe how to break down large numbers of screening hits and we provide a comprehensive overview of the strengths and weaknesses for each structural class. The overall profile (e.g. ligand efficiency, selectivity and ADME-Tox) is the distinctive feature that will define the priority for follow-up.

  16. Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection

    Science.gov (United States)

    Dudley, Matthew Z.; Sheen, Patricia; Gilman, Robert H.; Ticona, Eduardo; Friedland, Jon S.; Kirwan, Daniela E.; Caviedes, Luz; Rodriguez, Richard; Cabrera, Lilia Z.; Coronel, Jorge; Grandjean, Louis; Moore, David A. J.; Evans, Carlton A.; Huaroto, Luz; Chávez-Pérez, Víctor; Zimic, Mirko

    2016-01-01

    Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)–positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58–92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures. PMID:27928075

  17. [Cost]effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study

    Directory of Open Access Journals (Sweden)

    Mattace-Raso Francesco US

    2011-08-01

    Full Text Available Background Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall. Methods/Design A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged ≥65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D, costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis. Discussion The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction. Trial Registration The trial is registered in the Netherlands Trial Register (NTR1593

  18. Post-surgical analgesia in rainbow trout: is reduced cardioventilatory activity a sign of improved animal welfare or the adverse effects of an opioid drug?

    Science.gov (United States)

    Gräns, Albin; Sandblom, Erik; Kiessling, Anders; Axelsson, Michael

    2014-01-01

    The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM), on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss) at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4-7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation.

  19. Post-surgical analgesia in rainbow trout: is reduced cardioventilatory activity a sign of improved animal welfare or the adverse effects of an opioid drug?

    Directory of Open Access Journals (Sweden)

    Albin Gräns

    Full Text Available The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM, on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4-7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation.

  20. Improvement of the green fluorescent protein reporter system in Leishmania spp. for the in vitro and in vivo screening of antileishmanial drugs.

    Science.gov (United States)

    Pulido, Sergio A; Muñoz, Diana L; Restrepo, Adriana M; Mesa, Carol V; Alzate, Juan F; Vélez, Iván D; Robledo, Sara M

    2012-04-01

    Development of new therapeutic approaches for leishmaniasis treatment requires new high throughput screening methodologies for the antileishmanial activity of the new compounds both in vitro and in vivo. Reporter genes as the GFP have become one of the most promissory and widely used tools for drug screening in several models, since it offers live imaging, high sensibility, specificity and flexibility; additionally, the use of GFP as a reporter gene in screening assays eliminates all the drawbacks presented in conventional assays and also those technical problems found using other reporter genes. The utility of the GFP as a reporter gene in drug screening assays with Leishmania parasites depends on the homogeneity and stability of the GFP transfected strains. Stable expression of the GFP in the Old World Leishmania species has been demonstrated using integration vectors; however, no reports exist yet about the success of this methodology in the New World species. Here we report the generation of New World Leishmania strains expressing the GFP protein from an integration vector, which replaces one copy of the 18S RNA in the chromosome with the GFP coding sequence by homologous recombination. We also prove that the expression of the integrated GFP is stable and homogeneous in the transfected parasites after months in culture without selective pressure or during its use in hamster infection assays. The fluorescent strains are useful for in vitro, ex vivo and in vivo drug screening assays since no considerable variations in virulence or infectivity where seen attributable to the genetic manipulation during both in vitro and in vivo infection experiments. The platform described here for drug testing assays based on the use of stable fluorescent Leishmania strains coupled to flow cytometry and fluorescent microscopy is more sensitive, more specific and faster than conventional assays used normally for the evaluation of compounds with potential antileishmanial activity.

  1. New drugs in gynecologic cancer.

    Science.gov (United States)

    Daud, A; Munster, P; Munster, P; Spriggs, D R

    2001-04-01

    The implementation of new drug treatments has improved the prognosis for advanced cancers of the cervix, uterus, and ovary. Platinum analogs are the most effective drugs in the treatment of ovarian cancer. Other drugs, such as oxaliplatin, have been proposed as a rational treatment of platinum refractory ovarian cancer. Epothilones are also being studied in clinical trials, as are histone deacetylase inhibitors. Several promising agents may soon receive Food and Drug Administration approval.

  2. Drug Facts

    Medline Plus

    Full Text Available ... Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts ... Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs ...

  3. Drugged Driving

    Science.gov (United States)

    ... Parents & Educators Children & Teens Search Connect with NIDA : Google Plus Facebook LinkedIn Twitter YouTube Flickr RSS Menu ... misuse of prescription drugs can make driving a car unsafe—just like driving after drinking alcohol. Drugged ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  5. Drug Facts

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    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  6. Drug Facts

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    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  7. Study Drugs

    Science.gov (United States)

    ... study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta Most people get study ... How Much Sleep Do I Need? Prescription Drug Abuse How to Make Homework Less Work Organizing Schoolwork & ...

  8. Drug Facts

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    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  10. Drugs (image)

    Science.gov (United States)

    ... Drugs for fever, cough, stuffy nose, runny nose, diarrhea, and allergies are common drugs which are especially helpful during times of illness. All medications should be kept out of the reach of children.

  11. Drug Facts

    Science.gov (United States)

    ... drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different people around me. To stop using marijuana, "Cristina" is making positive changes in her life. She finds support from ...

  12. Reinforcing the Financial Management of Drug and Improving the Economic Efficiency in the Hospital%加强药品财务管理提高医院经济效益

    Institute of Scientific and Technical Information of China (English)

    史秀芳

    2012-01-01

    医院的流动资产中药品占具相当大的比重,药品是医院开展正常医疗业务工作不可缺少的物质保障.加强药品的财务管理,是确保医院会计信息准确性的基础,是领导进行决策的依据,是医院提高社会效益和经济效益的需要.%Drug, taking up large proportion of the liquid assets, serves as a necessary material safeguard for the normal medical business in the hospital. Strengthening drug management is not only the foundation ensuring the accuracy of the accounting information, the factor based on leaders' decisions, but also the necessity of improving both social and economic benefit.

  13. Epigenetic Drugs for Multiple Sclerosis.

    Science.gov (United States)

    Peedicayil, Jacob

    2016-01-01

    There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS.

  14. Four cases of Japanese patients with psoriatic arthritis in whom effective treatments by anti-tumor necrosis factor-α drugs were evaluated by magnetic resonance imaging together with improvement of skin lesions.

    Science.gov (United States)

    Yonenaga, Takenori; Saeki, Hidehisa; Nakagawa, Hidemi; Fukuchi, Osamu; Umezawa, Yoshinori; Hayashi, Mitsuha; Ito, Toshihiro; Yanaba, Koichi; Tojyo, Shinjiro; Fukuda, Kunihiko

    2015-01-01

    Because psoriatic skin lesions of psoriatic arthritis (PsA) usually precede the onset of joint symptom, dermatologists are in an ideal position to screen and find individuals with PsA early in the disease course. There have been no reports from the dermatology field evaluating the effect of anti-tumor necrosis factor (TNF)-α drugs on joint disorders using magnetic resonance imaging (MRI) in PsA patients. The purpose of this study was to elucidate the effectiveness of MRI in the evaluation of anti-TNF-α drugs on joint disease of Japanese PsA patients. Data were collected from four adult Japanese male PsA patients. MRI of the affected hand was performed at baseline and 1-7 months after infliximab or adalimumab treatment. T1 -weighted gadolinium-enhanced images with fat suppression were acquired in the coronal, sagittal and/or axial planes. We determined the apparent improvement of synovitis, periarticular inflammation, tenosynovitis and/or bone marrow edema by MRI after anti-TNF-α treatments in all the patients together with the improvement of skin lesions. We also determined in one patient that these symptoms detected by MRI before treatment were alleviated within 1 month and had disappeared 6 months after treatment, suggesting the potentially early detection of the effect of anti-TNF-α drugs on joint disease. We present four cases of Japanese patients with PsA in whom effective treatments by anti-TNF-α drugs were evaluated by contrast-enhanced MRI. This imaging enables dermatologists and radiologists to assess and monitor early inflammatory changes, and to grant PsA patients earlier access to modern treatment such as biologics.

  15. Drug Facts

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    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to ...

  16. Why do we take drugs? From the drug-reinforcement theory to a novel concept of drug instrumentalization.

    Science.gov (United States)

    Spanagel, Rainer

    2011-12-01

    The drug-reinforcement theory explains why humans get engaged in drug taking behavior. This theory posits that drugs of abuse serve as biological rewards by activating the reinforcement system. Although from a psychological and neurobiological perspective this theory is extremely helpful, it does not tell us about the drug-taking motives and motivation of an individual. The definition of drug instrumentalization goals will improve our understanding of individual drug-taking profiles.

  17. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  18. 限制性价格管制、经济福利和基本药物制度的帕累托改进%Ceiling Price, Economic Welfare and Pareto Improvement of Essential Drug System

    Institute of Scientific and Technical Information of China (English)

    贾洪波; 刘玮玮

    2011-01-01

    新一轮医药卫生体制改革对基本药物实施限制性价格管制措施.在完全竞争市场条件下政府对基本药物的限制性价格管制,把部分生产者剩余,转化为消费者剩余,导致了经济福利的净损失.现实世界中对基本药物实施限制性价格管制,是为了应对一定程度的基本药物市场失灵和政府对基本药物消费者剩余的评价高于对生产者剩余的评价.限制性价格管制对降低基本药物价格和增加其有效需求起到了积极作用,同时也凸显出基本药物供给短缺压力和加强公共财政责任的必要性.在实施限制性价格管制的前提下,基本药物制度应该在不断总结试点经验的基础上实施帕累托改进.%Ceiling price regulating measure to essential drugs has been implemented in the new round health system reform. Under the perfect competition market, the ceiling price of government regulating measure to essential drugs will transfer the part producer surplus to consumer surplus, leading to the net loss of economic welfare. The reasons that implementing the ceiling price to essential drugs in the real world are on the one side to response the market failure of essential drugs caused by some market monopoly, information asymmetry and positive externality, and on the other side to give consumer surplus of essential drugs the higher evaluation than to give producer surplus of essential drags. Ceiling price played the positive role to decrease the price of essential drugs and to increase the effective demand, and to stand out the shortage pressure of essential drags supply and the necessity to strengthen the public financial responsibility. Under the condition of ceiling price, essential drug system should implement the Pareto improvement based on summing up the pilot experience.

  19. Computational drug discovery

    Institute of Scientific and Technical Information of China (English)

    Si-sheng OU-YANG; Jun-yan LU; Xiang-qian KONG; Zhong-jie LIANG; Cheng LUO; Hualiang JIANG

    2012-01-01

    Computational drug discovery is an effective strategy for accelerating and economizing drug discovery and development process.Because of the dramatic increase in the availability of biological macromolecule and small molecule information,the applicability of computational drug discovery has been extended and broadly applied to nearly every stage in the drug discovery and development workflow,including target identification and validation,lead discovery and optimization and preclinical tests.Over the past decades,computational drug discovery methods such as molecular docking,pharmacophore modeling and mapping,de novo design,molecular similarity calculation and sequence-based virtual screening have been greatly improved.In this review,we present an overview of these important computational methods,platforms and successful applications in this field.

  20. 我院处方评价工作对提高安全用药的实践%Our Work to Improve the Safety Evaluation of Prescription Drugs of Practice

    Institute of Scientific and Technical Information of China (English)

    张芳

    2011-01-01

    目的:通过对处方对评价提高我院用药安全.方法:抽取我院2009年门诊处方,按每月随机抽出100张,根据对规定要求,按项目挑选出不合格处方进行归类.结果:经统计分析,填写评价处方表并上报发现的问题,提出处方改进建议,提高医师处方质量.结论:通过处方评价点评工作,使医师意识到处方的书写不规范,给用药安全带来很多隐患.建立处方的点评制度,规范处方书写,提高处方质量,防止差错,促进合理用药,保障用药安全.%Objective:Through a prescription for the safety of medication use of our hospital tremendously. Methods:Extraction of our outpatient prescription in 2009,a monthly random spare 100 votes, according to the regulations prescribed for measures for the administration of request, according to the project selected unqualified prescription categorize. Results:Through analysis, filed in evaluation and report to found the prescription table prescription problems,this paper put forward Suggestions to improve quality of doctors,improving prescription. Conclusion:Through comments on work,make prescription evaluation of doctors realized prescription for writing is not standard,drug safety brought many hidden problems. Establish the comment system, regulating the prescription,improve quality of prescription writing prescriptions, to prevent discrepancies,promote the rational drug use,guarantee safe drug use.

  1. Genetic polymorphisms and drug metabolism

    Directory of Open Access Journals (Sweden)

    Vita Dolžan

    2007-12-01

    Full Text Available Background: It is estimated that genetic factors account for 15–30 % of variability in drug response, however for some drugs this may be the major determinant in drug response. Pharmacogenetics aims to identify genetic sources of variability in response to drugs by studying genetic variations affecting drug metabolizing enzymes, transporters and drug targets thus causing interindividual variability in drug levels (pharmacokinetics, drug response (pharmacodynamics and side effects. Extensive information on genetic variability in drug metabolizing enzymes, transporters and targets is available from public databases. Drugs are metabolized in two phases. In Phase I drug is metabolically activated to reactive electrophilic form, mostly by cytochromes P450 (CYPs, to be conjugated to some endogenous compound by Phase II enzymes: UDP-glucuronosyltransferases (UGTs, N-acetyl-transferases (NATs, glutathione S-transferases (GSTs, or others. Genetic polymorphism of many enzymes involved in this process leads to inter-individual variations in metabolism and pharmacokinetics of drugs and could therefore influence drug response. Genetic polymorphism is the occurrence of two or more alleles at a given locus of which the rare allele has a frequency of at least 1 % or more in a given population. The understanding of a patient’s genotype and its corresponding effect on drug response could help distinguish between responders and non-responders of a specific drug treatment and help to choose the most effective drug and optimal dose. A large number of different methodologies have been developed for genotyping, however at present predictive genotyping for drug metabolizing enzymes does not occur routinely in the clinical practice.Conclusions: There is increasing evidence that genotyping for polymorphic drug metabolizing enzymes, in particular CYPs has potential to improve drug therapy and achieve higher response rates and reduced adverse effects. Open questions

  2. Preparation of biocompatible heat-labile enterotoxin subunit B-bovine serum albumin nanoparticles for improving tumor-targeted drug delivery via heat-labile enterotoxin subunit B mediation.

    Science.gov (United States)

    Zhao, Liang; Su, Rongjian; Cui, Wenyu; Shi, Yijie; Liu, Liwei; Su, Chang

    2014-01-01

    Heat-labile enterotoxin subunit B (LTB) is a non-catalytic protein from a pentameric subunit of Escherichia coli. Based on its function of binding specifically to ganglioside GM1 on the surface of cells, a novel nanoparticle (NP) composed of a mixture of bovine serum albumin (BSA) and LTB was designed for targeted delivery of 5-fluorouracil to tumor cells. BSA-LTB NPs were characterized by determination of their particle size, polydispersity, morphology, drug encapsulation efficiency, and drug release behavior in vitro. The internalization of fluorescein isothiocyanate-labeled BSA-LTB NPs into cells was observed using fluorescent imaging. Results showed that BSA-LTB NPs presented a narrow size distribution with an average hydrodynamic diameter of approximately 254±19 nm and a mean zeta potential of approximately -19.95±0.94 mV. In addition, approximately 80.1% of drug was encapsulated in NPs and released in the biphasic pattern. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that BSA-LTB NPs exhibited higher cytotoxic activity than non-targeted NPs (BSA NPs) in SMMC-7721 cells. Fluorescent imaging results proved that, compared with BSA NPs, BSA-LTB NPs could greatly enhance cellular uptake. Hence, the results indicate that BSA-LTB NPs could be a potential nanocarrier to improve targeted delivery of 5-fluorouracil to tumor cells via mediation of LTB.

  3. Improvement in the water solubility of drugs with a solid dispersion system by spray drying and hot-melt extrusion with using the amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and d-mannitol.

    Science.gov (United States)

    Ogawa, Noriko; Hiramatsu, Tomoki; Suzuki, Ryohei; Okamoto, Ryohei; Shibagaki, Kohei; Fujita, Kosuke; Takahashi, Chisato; Kawashima, Yoshiaki; Yamamoto, Hiromitsu

    2017-09-08

    The aim of this study was to prepare and characterize solid dispersion particles with a novel amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, as a water-soluble carrier. Solid dispersion particles were prepared by hot-melt extrusion and spray drying. Indomethacin (IMC) was used as a model comprising drugs with low solubility in water and d-mannitol (MAN) was used as an excipient. The physicochemical properties of prepared particles were characterized by scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, FTIR spectra analysis, and drug release studies. Stability studies were also conducted under stress conditions at 40°C, 75% relative humidity. We found that dissolution behavior of the original drug crystal could be improved by solid dispersion with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer. The PXRD pattern and thermal analysis indicated that the solid dispersion prepared with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC was in an amorphous state. FTIR spectra analysis indicated that the interaction manner between the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC may differ with the preparation method and formulation of solid dispersions. Stability studies proved that the amorphous state of IMC in solid dispersion particles was preserved under stress conditions for more than two weeks. Copyright © 2017. Published by Elsevier B.V.

  4. Discussion on the Experience of Improving Account Coincidence Rate of Hospital Drug Stocktaking%提高医院药品盘点账物相符率的经验浅谈

    Institute of Scientific and Technical Information of China (English)

    袁忠伟

    2015-01-01

    The account coincidence rate of drug inventory is one of the important indexes to judge the quality of drug management of pharmacy department. In this article, based on the investigation of the reasons of account discrepancy rate by computer system of pharmacy department, it was suggested that measures should be taken to improve the account coincidence rate such as the establishment of strict award and penalty system, divisional man-agement of stock drugs, dedicated management, strict control of stocktaking, warehouse entry and delivery, etc..%药品盘点的账物相符率是财务衡量药剂科药品管理工作的重要指标之一。本文通过药房计算机系统运行各个环节查找账物不相符的原因,指出应通过严格奖惩制度,对药房货架库存药品分区管理,专人管理,严把盘点、出库、入库关等环节,提高账物相符率。

  5. Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study.

    Science.gov (United States)

    Akdemir, Gülşah; Heimans, Lotte; Bergstra, Sytske Anne; Goekoop, Robbert J; van Oosterhout, Maikel; van Groenendael, Johannes H L M; Peeters, André J; Steup-Beekman, Gerda M; Lard, Leroy R; de Sonnaville, Peter B J; Grillet, Bernard A M; Huizinga, Tom W J; Allaart, Cornelia F

    2017-09-28

    To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. In 12 hospitals, 610 patients with early (25 points in 5 years. Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. 中药活血化淤法改善脑出积压患者运动功能疗效观察%Observation of improvement of movement function by Chinese drugs through promoting circulation by removing blood stasis in patients with brain hemorrhage

    Institute of Scientific and Technical Information of China (English)

    尹德铭; 高聪; 沈岩松

    2002-01-01

    @@ Background:Disability rate following brain hemorrhage is high.Rcovery and improvement of movement function is closely related to management of brain hemorrhage during acute phage,absorption of hematoma.According to traditional medicine principle,Chinese drugs promote absorption and functional recovery through promoting blood circulation by removing blood stasis.The Chinese drugs are safe in clinic

  7. 监管与提高:由“药儿园”引发的思考%Regulation and Improvement:Reflections by"Drug Kindergarten"

    Institute of Scientific and Technical Information of China (English)

    李焕霞

    2015-01-01

    近来湖北、陕西和吉林三省相继出现幼儿园在未告知家长的情况下给幼儿喂食“病毒灵”事件,引起社会极大关注。幼儿园本是孩子健康成长的乐园却出现种种乱象变成“药儿园”,一时激起家长以及相关部门的问责。从国家有关部门监管不力和“药儿园”自身办学严重失范两方面分析找出措施:国家加大对学前教育的投入、监管力度和幼儿园自身要提高办园水平,最终还幼儿园一方净土。%Recently, Hubei, Shaanxi and Jilin provinces have appeared kindergarten delivering a baby"virus of Hope"event without telling parents aroused great concern. The nursery is a paradise for the healthy growth of children, but there are all sorts of chaos into a"drug kindergarten", and sometimes provoke parents and relevant departments accountable. Supervision from the national authorities and the"drug children garden"anomie serious analysis to identify two aspects of running their own measures:the state has increased investment in pre-school education, supervision and kindergarten Office Park to raise the level of their own, ultimately kindergarten pure land.

  8. Innovative drug delivery nanosystems improve the anti-tumor activity in vitro and in vivo of anti-estrogens in human breast cancer and multiple myeloma.

    Science.gov (United States)

    Maillard, Sébastien; Ameller, Thibault; Gauduchon, Juliette; Gougelet, Angélique; Gouilleux, Fabrice; Legrand, Philippe; Marsaud, Véronique; Fattal, Elias; Sola, Brigitte; Renoir, Jack-Michel

    2005-02-01

    Anticancer drug efficiency is governed by its bioavailability. In order to increase this parameter, we synthesized several injectable and biodegradable systems based on incorporation of anti-estrogens (AEs) in nanoparticles (NPs) and liposomes were synthesized. Both nanospheres (NS) and nanocapsules (NCs, polymers with an oily core in which AEs were solubilized) incorporated high amounts of 4-hydroxy-tamoxifen (4-HT) or RU 58668 (RU). Physico-chemical and biological parameters of these delivery systems, and coupling of polyethylene-glycol chains on the NP surface revealed to enhance the anti-tumoral activity of trapped AEs in a breast cancer MCF-7 cell xenograft model and to induce apoptosis. These features correlated with an augmentation of p21(Waf-1/Cip1) and of p27(Kip1) and a concomitant decrease of cyclin D1 and E in tumor extracts. Liposomes containing various ratios of lipids enhanced the apoptotic activity of RU in several multiple myeloma (MM) cell lines tested by flow cytometry. MM cell lines expressed both estrogen receptor alpha and beta subtypes except Karpas 620. Karpas 620 cells which did not respond to AEs became responsive following ER cDNA transfection. A new MM xenograft model was generated after s.c. injection of RPMI 8226 cells in nude mice. RU-loaded liposomes, administered i.v. in this model, at a dose of 12mgRU/kg/week, induced the arrest of tumor growth contrary to free RU or to empty liposomes. Thus, the drug delivery of anti-estrogens enhances their ability to arrest the growth of tumors which express estrogen receptors and are of particular interest for estrogen-dependent breast cancer treatment. In addition it represents a new potent therapeutic approach for multiple myeloma.

  9. Application of Platonic Analysis for Improving Rational Drug Use in Our Hospital%柏拉图分析法在提高我院临床合理用药水平中的应用

    Institute of Scientific and Technical Information of China (English)

    徐萌; 郭凤霞; 司法启; 梁立峰; 倪惠珍; 王海玲

    2013-01-01

    目的:降低不合理用药率,提高临床合理用药水平.方法:选取我院588名医师2010年第1、2季度病历共2 940份,采用柏拉图分析法对其中的不合理用药情况进行解析,找出关键的影响因素,采取切实可行的应对措施,再与改进后的2011年第1、2季度的2 940份病历相关情况进行比较.结果:我院不合理用药的类型包括用药时机不当、用药疗程不当等,并主要体现在围手术期用药时,影响因素涉及未及时进行病原学检查和药敏试验、未区分预防和治疗用药等;通过采取提高认识、知识培训、完善资料等措施,不合理用药发生频数由改进前的4 003例次下降到1 814例次,不合理用药分类的15项中有13项指标显著下降(P<0.05).结论:柏拉图分析法可量化临床药师各项活动和考评临床药学服务效果,可提高医院临床合理用药水平.%OBJECTIVE: To reduce the incidence of irrational drug use and improve rational use of drugs in the clinic. METHODS: 2 940 medical records were collected from 588 physicians of our hospital in the first and second quarter of 2010. Irrational drug use was analyzed by Platonic analysis to find out important influential factors and carry out the feasible corresponding measures, and then compared with 2 940 medical records collected in the first and second quarter of 2011. RESULTS: Irrational drug use of our hospital included inappropriate medication time, improper treatment course, and so on, which was mainly reflected in aspect of perioperative medication; influential factors involved etiological examination and drug sensitive test behind time, confusion between prophylactic medication and therapeutic medication, etc. After enhancing understanding, training, perfecting information and other measures, the number of irrational drug use decreased from 4 003 to 1 814, and that of 13 items decreased sharply among 15 items of irrational drug use (P<0.05). CONCLUSIONS: Platonic

  10. How to improve communication for the safe use of medicines?: Discussions on social marketing and patient-tailored approaches at the annual meetings of the WHO Programme for International Drug Monitoring.

    Science.gov (United States)

    Bahri, Priya; Harrison-Woolrych, Mira

    2012-12-01

    Over the past decade, the annual meetings of national centres participating in the WHO Programme for International Drug Monitoring have increasingly included discussions on how to improve communication between national pharmacovigilance centres, patients, healthcare professionals, policy makers and the general public, with the aim of promoting the safe use of medicines. At the most recent meetings, working groups were dedicated to discuss possible applications and implementation of social marketing and patient-tailored approaches. This article provides the history and a summary of the recent discussions and recommendations to support progress in this respect at national and global level. Recommendations are made to investigate and pilot these approaches in small-scale projects at national pharmacovigilance centres. Applying elements from the social marketing and patient-tailored approaches to support behaviours of safe medicines use in patients and healthcare professionals should give the pharmacovigilance community new tools to achieve their goal to minimize risks with medicines and improve patient safety.

  11. 基于拉曼光谱的改进投影算法快速鉴别药品%Fast Discrimination of Drugs by Improved Projection Algorithm Based on Raman Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    贾南南; 季江; 高鹏飞; 阮斌; 陶振强; 李龙潭; 李骁; 郭汉明

    2015-01-01

    The projection algorithm used in mixture analysis to determine whether there is unknown disturbance existing in grey system can not accurately identify different samples and similar samples at the same time when it is used in the identification of drugs ,because of the insufficient criteria .In the present study ,one of its criteria for whether the size of measurement error of testing sample is at a limited level is improved for whether the size and distribution of measurement error is equal and similar between testing sample and standard sample .By testing 6 kinds of normal drugs (including BAYER Aspirin Enteric-coated Tablets ,TYLENOL Acetaminophen Sustained Release Tablets ,BAYER Compound Paracetamol Tablets(Ⅱ ) ,HUAZHONG Compound Vitamin C ,HUAZHONG Vitamin B and MADINGLIN Demperidone Tablets) and 3 kinds of similar drugs of aspirin (including BAYER Aspirin Enteric-coated Tablets ,Shanghai SINE Aspirin Enteric-coated Tablets and Bamyl Aspirin Efferves-cent Tablets) ,it was found that the un-improved projection algorithm directly used in discrimination of drugs shows poor per-formance with many problems existing ,however ,the improved projection algorithm can discriminate different drugs and similar drugs with accuracy up to 100% .The improved projection algorithm can be a universal ,accurate and reliable automated pharma-ceutical identification algorithm and can provide a reference for the study on identification of substance .%投影算法常用于混合物分析中确定灰色体系是否存在未知干扰,而在用于药品鉴别时,由于其判定标准不充分,故不能同时准确鉴别不同药品和相似药品。提出将投影算法的判定标准(待测物质光谱的量测误差大小是否在限定水平)改进为待测物质光谱与标准物质光谱的量测误差大小水平是否相当、量测误差分布是否相近。将改进投影算法与未经改进投影算法用于六种(拜耳阿司匹林肠溶片、泰诺对乙酰氨

  12. Nanosuspension Technology for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jiraporn CHINGUNPITUK

    2007-06-01

    Full Text Available The poor water solubility of drugs is major problem for drug formulation. To date, nanoscale systems for drug delivery have gained much interest as a way to improve the solubility problems. The reduction of drug particles into the sub-micron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are promising candidates that can be used for enhancing the dissolution of poorly water soluble drugs. Nanosuspensions contain submicron colloidal dispersion of pharmaceutical active ingredient particles in a liquid phase stabilized by surfactants. Production of drugs as nanosuspensions has been developed for drug delivery systems as an oral formulation and non-oral administration. This review describes the methods of pharmaceutical nanosuspension production, formulations and pharmaceutical applications in drug delivery as well as the marketed products.

  13. CONTROLLED DRUG DELIVERY THROUGH MICROENCAPSULATION

    Directory of Open Access Journals (Sweden)

    NIKHIL K. SACHAN

    2006-01-01

    Full Text Available An appropriately designed controlled release drug delivery system can be a major advance towards solving problems concerning to the targeting of drug to a specific organ or tissue and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

  14. Combined analysis of pharmacokinetic and efficacy data of preclinical studies with statins markedly improves translation of drug efficacy to human trialss

    NARCIS (Netherlands)

    Steeg, E. van de; Kleemann, R.; Jansen, H.T.; Duyvenvoorde, W. van; Offerman, E.H.; Wortelboer, H.M.; DeGroot, J.

    2013-01-01

    Correct prediction of human pharmacokinetics (PK) and the safety and efficacy of novel compounds based on preclinical data, is essential but often fails. In the current study, we aimed to improve the predictive value of ApoE*3Leiden (E3L) trans-genic mice regarding the cholesterol-lowering efficacy

  15. Club Drugs

    Science.gov (United States)

    ... Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults ...

  16. Finding parasites and finding challenges: improved diagnostic access and trends in reported malaria and anti-malarial drug use in Livingstone district, Zambia

    Directory of Open Access Journals (Sweden)

    Masaninga Freddie

    2012-10-01

    Full Text Available Abstract Background Understanding the impact of malaria rapid diagnostic test (RDT use on management of acute febrile disease at a community level, and on the consumption of anti-malarial medicines, is critical to the planning and success of scale-up to universal parasite-based diagnosis by health systems in malaria-endemic countries. Methods A retrospective study of district-wide community-level RDT introduction was conducted in Livingstone District, Zambia, to assess the impact of this programmed on malaria reporting, incidence of mortality and on district anti-malarial consumption. Results Reported malaria declined from 12,186 cases in the quarter prior to RDT introduction in 2007 to an average of 12.25 confirmed and 294 unconfirmed malaria cases per quarter over the year to September 2009. Reported malaria-like fever also declined, with only 4,381 RDTs being consumed per quarter over the same year. Reported malaria mortality declined to zero in the year to September 2009, and all-cause mortality declined. Consumption of artemisinin-based combination therapy (ACT dropped dramatically, but remained above reported malaria, declining from 12,550 courses dispensed by the district office in the quarter prior to RDT implementation to an average of 822 per quarter over the last year. Quinine consumption in health centres also declined, with the district office ceasing to supply due to low usage, but requests for sulphadoxine-pyrimethamine (SP rose to well above previous levels, suggesting substitution of ACT with this drug in RDT-negative cases. Conclusions RDT introduction led to a large decline in reported malaria cases and in ACT consumption in Livingstone district. Reported malaria mortality declined to zero, indicating safety of the new diagnostic regime, although adherence and/or use of RDTs was still incomplete. However, a deficiency is apparent in management of non-malarial fever, with inappropriate use of a low-cost single dose drug, SP

  17. Drug therapy for improving walking distance in intermittent claudication: a systematic review and meta-analysis of robust randomised controlled studies

    DEFF Research Database (Denmark)

    Momsen, A H; Jensen, Martin Bach; Norager, C B

    2009-01-01

    of the databases to February 2009. In addition, reference lists were manually searched. REVIEW METHODS: Based upon a power calculation, only robust (n>56), peer-reviewed, double-blinded, randomised and placebo-controlled trials were included. The main outcomes evaluated were maximal walking distance (MWD) and pain......-free walking distance on a treadmill. Random models were used in the statistical analysis, and chi-square test were used to test for heterogeneity. RESULTS: Among 220 trials, only 43 trials fulfilled the quality criteria. Treatment periods, follow-up and treadmill protocols varied substantially. Vasodilator...... agents and phosphodiesterase inhibitors show robust significant results compared to placebo, but the improvements in MWD are modest. The highest benefit was caused by lipid-lowering agents, which in mean gained above 160 m in MWD, while the other agents only improved MWD about 50 m. CONCLUSION: Several...

  18. Improved efficacy of a novel anti-angiogenic drug combination (TL-118) against colorectal-cancer liver metastases; MRI monitoring in mice.

    Science.gov (United States)

    Edrei, Y; Gross, E; Corchia, N; Abramovitch, R

    2012-08-07

    The poor prognosis of patients with colorectal-cancer liver metastases (CRLM) and the insufficiency of available treatments have raised the need for alternative curative strategies. We aimed to assess the therapeutic potential of TL-118, a new anti-angiogenic drug combination, for CRLM treatment, in a mouse model. The therapeutic potential of TL-118 was evaluated and compared with B20-4.1.1 (B20; anti-VEGF antibody) and rapamycin in CRLM-bearing mice. Tumour progression and the vascular changes were monitored by MRI. Additionally, mice survival, cell proliferation, apoptosis and vessel density were evaluated. This study demonstrated an unequivocal advantage to TL-118 therapy by significantly prolonging survival (threefold) and reducing metastasis perfusion and vessel density (ninefold). The underlying mechanism for TL-118-treatment success was associated with hepatic perfusion attenuation resulting from reduced nitric-oxide (NO) serum levels as elucidated by using hemodynamic response imaging (HRI, a functional MRI combined with hypercapnia and hyperoxia). Further, systemic hepatic perfusion reduction during the initial treatment phase by adding NO inhibitor has proven to be essential for reaching maximal therapeutic effects for both TL-118 and B20. TL-118 harbours a potential clinical benefit to CLRM patients. Moreover, the reduction of hepatic perfusion at early stages of anti-angiogenic therapies by adding NO inhibitor is crucial for achieving maximal anti-tumour effects.

  19. Improving the drug delivery characteristics of graphene oxide based polymer nanocomposites through the "one-pot" synthetic approach of single-electron-transfer living radical polymerization

    Science.gov (United States)

    Gao, Peng; Liu, Meiying; Tian, Jianwen; Deng, Fengjie; Wang, Ke; Xu, Dazhuang; Liu, Liangji; Zhang, Xiaoyong; Wei, Yen

    2016-08-01

    Graphene oxide (GO) based polymer nanocomposites have attracted extensive research interest recently for their outstanding physicochemical properties and potential applications. However, surface modification of GO with synthetic polymers has demonstrated to be trouble for most polymerization procedures are occurred under non-aqueous solution, which will in turn lead to the restacking of GO. In this work, a facile and efficient "one-pot" strategy has been developed for surface modification of GO with synthetic polymers through single-electron-transfer living radical polymerization (SET-LRP). The GO based polymer nanocomposites were obtained via SET-LRP in aqueous solution using poly(ethylene glycol) methyl ether methacrylate (PEGMA) as the monomer and 11-bromoundecanoic acid as the initiator, which could be effectively adsorbed on GO through hydrophobic interaction. The successful preparation of GO based polymer nanocomposites was confirmed by a series of characterization techniques such as 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. The resultant products exhibit high water disperisibility, excellent biocompatibility and high efficient drug loading capability, making these PEGylated GO nanocomposites promising candidates for biomedical applications.

  20. Herbal drugs and drug interactions

    OpenAIRE

    Gül Dülger

    2014-01-01

    Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects. Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices.In the present study, pharmacokinetic and pharmacodynamic interactions ...

  1. Drugged Driving

    Science.gov (United States)

    ... Age Adults in 2015 Teens and E-cigarettes Abuse of Prescription (Rx) Drugs Affects Young Adults Most Substance Use in Women and Men View All NIDA's Publication Series Brain Power DrugFacts Mind Over Matter Research Reports NIDA Home ...

  2. Drug treatment

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010263 Drug resistance mechanism of non-small cell lung cancer PC9/AB2 cell line with acquired drug resistance to gefitinib.JU Lixia(鞠立霞),et al. Dept Oncol,Shanghai Pulm Hosp,Tongji Univ,Shanghai 200433. Chin J Tuberc Respir Dis 2010;33(5):354-358. Objective To

  3. Drug Education.

    Science.gov (United States)

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  4. Drug abuse in athletes

    Directory of Open Access Journals (Sweden)

    Reardon CL

    2014-08-01

    Full Text Available Claudia L Reardon, Shane Creado Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Abstract: Drug abuse occurs in all sports and at most levels of competition. Athletic life may lead to drug abuse for a number of reasons, including for performance enhancement, to self-treat otherwise untreated mental illness, and to deal with stressors, such as pressure to perform, injuries, physical pain, and retirement from sport. This review examines the history of doping in athletes, the effects of different classes of substances used for doping, side effects of doping, the role of anti-doping organizations, and treatment of affected athletes. Doping goes back to ancient times, prior to the development of organized sports. Performance-enhancing drugs have continued to evolve, with “advances” in doping strategies driven by improved drug testing detection methods and advances in scientific research that can lead to the discovery and use of substances that may later be banned. Many sports organizations have come to ban the use of performance-enhancing drugs and have very strict consequences for people caught using them. There is variable evidence for the performance-enhancing effects and side effects of the various substances that are used for doping. Drug abuse in athletes should be addressed with preventive measures, education, motivational interviewing, and, when indicated, pharmacologic interventions. Keywords: doping, athletes, steroids, drug abuse, mental illness

  5. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh

    2011-01-01

    Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.

  6. Non-biologic disease-modifying antirheumatic drugs (DMARDs) improve pain in inflammatory arthritis (IA): a systematic literature review of randomized controlled trials.

    Science.gov (United States)

    Steiman, Amanda J; Pope, Janet E; Thiessen-Philbrook, Heather; Li, Lihua; Barnabe, Cheryl; Kalache, Fares; Kung, Tabitha; Bessette, Louis; Flanagan, Cathy; Haraoui, Boulos; Hochman, Jacqueline; Leclercq, Sharon; Mosher, Dianne; Thorne, Carter; Bykerk, Vivian

    2013-05-01

    Evidence supports early use of non-biologic DMARDs to prevent irreversible damage in inflammatory arthritides, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and possibly ankylosing spondylitis (AS). However, there is a paucity of data exploring their effects on pain as a primary outcome in these conditions. This systematic literature review investigated the effect of non-biologic DMARDs on pain levels in IA and examined whether disease duration impacted efficacy. We searched Medline, Embase, Cochrane Central, and Cochrane Database of Systematic Reviews, abstracts from the 2008 to 2010 American College of Rheumatology annual congresses, and citation lists of retrieved publications. Only randomized, double-blind controlled trials were analyzed. Quality was assessed with the Risk of Bias tool. Descriptive statistics were used in meta-analysis. 9,860 articles were identified, with 33 eligible for inclusion: 8 in AS, 6 in PsA, 9 in early RA (ERA), and 10 in established RA. In ERA and established RA, all studies of DMARDs (monotherapy and combination therapies) consistently revealed statistically significant reductions in pain except three oral gold studies. In AS, sulfasalazine studies showed significant pain reduction, whereas use of other DMARDs did not. In PsA, 5 of 6 studies reported VAS-pain improvement. From the studies included, we were unable to assess the influence of disease duration on pain outcomes in these rheumatic conditions. DMARDs improve pain in early and established RA. Sulfasalazine may improve pain in AS and PsA. Further study is needed to assess the relationship between disease duration and DMARD efficacy in reducing pain in these conditions.

  7. The application of quality control circles for nurses in improving the use of chemotherapy drugs awareness%品管圈在提高护士对使用化疗药物知晓率中的应用

    Institute of Scientific and Technical Information of China (English)

    胡艳兴; 陈晓敏; 夏娜; 欧敏仪; 张瑞燕; 李珍文

    2016-01-01

    目的:探讨品管圈活动对护士使用常用化疗药物知晓的应用效果。方法:选取2013年1月~2015年1月本科室护理人员24名为研究对象,2014年9月成立品管圈小组,通过主题选定、计划拟定、现状把握、目标设定、要因分析、拟定对策并实施。结果:开展品管圈活动后,护士对常用化疗药物相关知识考核成绩明显高于实施前,差异有统计学意义(P ﹤0.05),无形成果显著。结论:将品管圈活动应用于护士对常用化疗药物使用的培训和管理,能有效提高其用药知识,保证护理安全。%Objective:To explore the application effect of quality control circle activities for nurses to use commonly known chemotherapy drugs. Methods:The choice of 24 undergraduate course room nursesfrom January 2013 to January 2015 was regarded as the research object. The quality control circlesteam was set up in September 2014 through topic selection,planning,current situation,goal setting,analysis,proposed countermeasures and performance. Results:The im-plementation of quality management circle activity significantly improved the assessment scores of the nurse to commonly use chemotherapy drugs than before, whose difference was statistically significant(P ﹤0. 05),with obvious intangible fruits. Conclusion:The application of qualitycircle activity to nurse training and management over the use of commonly used chemotherapy drugs,can effectively improve their knowledge of drugs and guarantee nursing safety.

  8. 三级综合医院门诊用药咨询特点分析及改善措施%Analysis of the Outpatient Drug Counseling Characteristics and the Improvement Measures in the Tertiary A Hospi-tals

    Institute of Scientific and Technical Information of China (English)

    张鹏; 杨海霞

    2015-01-01

    Objective To analyze the characteristics of the tertiary general hospital's outpatient medication consultation enhance the level of pharmaceutical care. Methods Statistical analysis of the outpatient pharmacy drug consultation records dur-ing 2012 -2014 in our hospital was performed by summarizing the characteristics of medication consultation. Results The drug consultation records in outpatient pharmacy increasing in last three years, consultants mainly distributed in the pediatrics, cardiol-ogy, gastroenterology and endocrinology, the mainly age was≥55 years and≤12 years old and the mainly drugs were cardiovas-cular, antibacterialand antidiabetic related. The main contents of consulting were usage and dosage and adverse drug reactions. Conclusion Pharmacists need to continuously strengthen and expand the knowledge of drugs according to the characteristics of medication consultation in our hospital, through various forms to carry out a full range of medication consultation service, and ef-fectively improve the patient feeling.%目的 分析三级综合医院门诊用药咨询特点,提高药学服务水平. 方法 对我院门诊药房2012年至2014年用药咨询记录进行统计分析,总结用药咨询特点. 结果 门诊药房近3年用药咨询服务不断增加,咨询患者就诊科室主要分布于儿科、心血管科、消化科及内分泌科等,咨询患者年龄以≥55岁及≤12岁为主;咨询药物主要为心血管药物、抗菌药物、降糖药物等;咨询的主要内容为用法用量及药物不良反应等. 结论 药师需要不断加强与扩大药物知识,根据门诊用药咨询特点,通过各种形式全方位开展用药咨询服务,切实改善患者就医感受.

  9. Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

    Science.gov (United States)

    Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

    2017-01-20

    Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.

  10. Improving survey methods in sero-epidemiological studies of injecting drug users: a case example of two cross sectional surveys in Serbia and Montenegro

    Directory of Open Access Journals (Sweden)

    Simić Milena

    2009-02-01

    Full Text Available Abstract Background Little is known about the prevalence of HIV or HCV in injecting drug users (IDUs in Serbia and Montenegro. We measured prevalence of antibodies to HIV (anti-HIV and hepatitis C virus (anti-HCV, and risk factors for anti-HCV, in community-recruited IDUs in Belgrade and Podgorica, and determined the performance of a parallel rapid HIV testing algorithm. Methods Respondent driven sampling and audio-computer assisted survey interviewing (ACASI methods were employed. Dried blood spots were collected for unlinked anonymous antibody testing. Belgrade IDUs were offered voluntary confidential rapid HIV testing using a parallel testing algorithm, the performance of which was compared with standard laboratory tests. Predictors of anti-HCV positivity and the diagnostic accuracy of the rapid HIV test algorithm were calculated. Results Overall population prevalence of anti-HIV and anti-HCV in IDUs were 3% and 63% respectively in Belgrade (n = 433 and 0% and 22% in Podgorica (n = 328. Around a quarter of IDUs in each city had injected with used needles and syringes in the last four weeks. In both cities anti-HCV positivity was associated with increasing number of years injecting (eg Belgrade adjusted odds ratio (AOR 5.6 (95% CI 3.2–9.7 and Podgorica AOR 2.5 (1.3–5.1 for ≥ 10 years v 0–4 years, daily injecting (Belgrade AOR 1.6 (1.0–2.7, Podgorica AOR 2.1 (1.3–5.1, and having ever shared used needles/syringes (Belgrade AOR 2.3 (1.0–5.4, Podgorica AOR 1.9 (1.4–2.6. Half (47% of Belgrade participants accepted rapid HIV testing, and there was complete concordance between rapid test results and subsequent confirmatory laboratory tests (sensitivity 100% (95%CI 59%–100%, specificity 100% (95%CI 98%–100%. Conclusion The combination of community recruitment, ACASI, rapid testing and a linked diagnostic accuracy study provide enhanced methods for conducting blood borne virus sero-prevalence studies in IDUs. The relatively high

  11. A high maintenance dose of clopidogrel improves short-term clinical outcomes in patients with acute coronary syndrome undergoing drug-eluting stent implantation

    Institute of Scientific and Technical Information of China (English)

    HAN Ya-ling; WANG Bin; LI Yi; XU Kai; WANG Shou-li; JING Quan-min; WANG Zu-lu; WANG Dong-mei; MA Ying-yan; WANG Geng

    2009-01-01

    Background Recurrent ischemic events occurred even during routine use of 75 mg clopidogrel in addition to aspirin,that indicated a potentially insufficient maintenance dosage of clopidogrel.The aim of the present study was to evaluate the short-term efficacy and safety of a 150 mg maintenance dose of clopidogrel following a 600 mg loading dose in patients with an acute coronary syndrome (ACS) undergoing drug eluting stent (DES) implantation.Methods Between November 2005 and November 2006,a total of 813 consecutive ACS patients undergoing DES implantation were enrolled.A 600 mg loading dose was administered before percutaneous coronary intervention (PCI) nd patients were randomized to receive clopidogrel 75 mg or 150 mg for 30 days in addition to 300 mg aspidn daily.Primary end points were the composite of cardiac death,non-fatal myocardial infarction (MI) and urgent target vessel revascularization (UTVR).Secondary end points included stent thrombosis (ST),major and minor bleeding events at 30days.Results At a follow-up period of 30 days,4 (1.0%) patients in the 150 mg group and 9 (2.2%) patients in the 75 mg group (P >0.05) reached the primary end points.There was no significant difference in the incidences of MI (0.5% vs1.2%,P >0.05),UTVR (0.7% vs 2.0%,P >0.05),and cardiac death (0.2% vs 0.2%,P >0.05) between the two groups.The incidence of ST (0 vs 1.5%,P <0.05) was significantly lower in the 150 mg group than that in the 75 mg group.There were no significant differences between both groups regarding the risk of major (0.2% vs 0,P >0.05) or minor (0.5% vs 0.2%,P >0.05) bleedings.Conclusion A high clopidogrel maintenance dose of 150 mg daily following a 600 mg loading dose for the first month after PCI procedure reduces the risk of ST and appears to be safe in patients with ACS undergoing DES implantation.

  12. Center for Drug Evaluation and Research

    Data.gov (United States)

    Federal Laboratory Consortium — The Center for Drug Evaluation and Research(CDER) performs an essential public health task by making sure that safe and effective drugs are available to improve the...

  13. Rational Prescribing in Primary care (RaPP: process evaluation of an intervention to improve prescribing of antihypertensive and cholesterol-lowering drugs

    Directory of Open Access Journals (Sweden)

    Oxman Andrew D

    2006-08-01

    Full Text Available Abstract Background A randomised trial of a multifaceted intervention for improving adherence to clinical practice guidelines for the pharmacological management of hypertension and hypercholesterolemia increased prescribing of thiazides, butdetected no impact onthe use of cardiovascular risk assessment toolsor achievement of treatment targets. We carried out a predominantly quantitative process evaluation to help explain and interpret the trial-findings. Methods Several data-sources were used including: questionnaires completed by pharmacists immediately after educational outreach visits, semi-structured interviews with physicians subjected to the intervention, and data extracted from their electronic medical records. Multivariate regression analyses were conducted to explore the association between possible explanatory variables and the observed variation across practices for the three main outcomes. Results The attendance rate during the educational sessions in each practice was high; few problems were reported, and the physicians were perceived as being largely supportive of the recommendations we promoted, except for some scepticism regarding the use of thiazides as first-line antihypertensive medication. Multivariate regression models could explain only a small part of the observed variation across practices and across trial-outcomes, and key factors that might explain the observed variation in adherence to the recommendations across practices were not identified. Conclusion This study did not provide compelling explanations for the trial results. Possible reasons for this include a lack of statistical power and failure to include potential explanatory variables in our analyses, particularly organisational factors. More use of qualitative research methods in the course of the trial could have improved our understanding.

  14. Organoclays for drug delivery Systems

    OpenAIRE

    Canovas Creus, Alba

    2008-01-01

    Modified clays can be used as carriers of drugs due to their suitable properties and structure in order to achieve improvements in drug delivery. The study of this thesis starts with an introduction to mineral clays and its classification, properties and characterization, then deepens into modified clays (properties, comparison with mineral clays, applications and procedure of modification). Another chapter is focused in drug delivery: definition, its difficulties nowadays and the different w...

  15. Clinical pharmacology of novel anticancer drug formulations

    OpenAIRE

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The majority of new anti-cancer drugs are oral pharmaceutical formulations, consisting of new chemical entities, like molecular targeted agents and novel variants of existing drugs. The development of oral ...

  16. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.

    2016-03-31

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Link Between Drug Use and HIV/AIDS Treatment & Recovery What is Treatment? Why Does a Person Need ... Work? What Are the Treatment Options? What Is Recovery? What Is a Relapse? How Can Friends and ...