Search results for: drug administration

Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Ian Walmsley

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The aim of this paper is to explore the influence of time and temporality on the experience of coming off heroin in prison. The presentation draws on qualitative data collected during a small-scale pilot study of the role of self-care in the process of coming off drugs in prison. Time and temporality emerged as a key theme in the interview transcripts. Drug dependent prisoners experience of time in prison has not been recognized in the research literature. Instead, the literature on prison time typically views prisoners as a homogenous group or tends to focus on the influence of aging and gender on prison time. Furthermore, there is a tendency in the literature on prison drug treatment and recovery to conceptualize drug dependent prisoners as passive recipients of prison healthcare, rather than active agents. In building on these gaps, this paper argues that drug dependent prisoners experience multiple temporalities which involve an interaction between the body-times of the drug dependent prisoner and the economy of time in prison. One consequence of this interaction is the feeling that they are doing, at this point in their prison sentence, double prison time. The second part of the argument is that time and temporality were a means through which they governed their withdrawing bodies. In addition, this paper will comment on the challenges of prison research in England.

Keywords: heroin withdrawal, time and temporality, prison, body

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Authors: Marcelus U. Ajonina, Deodata B. Ngonga, Kenric B. Ware, Carine K. Nfor

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Background: Lack of knowledge of rational use of antimalarial drugs among dispensers is a serious problem, especially in areas of intense transmission, thus increasing the risk of resistance and adverse drug reactions. This study was aimed at assessing the knowledge of malaria as well as perception and dispensing practices of antimalarials among vendors in Buea community. Methods: A community-based cross-sectional survey of a random sample of 140 drug vendors living within the Buea community was conducted between March and June 2017. A questionnaire was designed to obtain information from drug vendors on the general knowledge of malaria as well as dispensing practices. Data were analyzed using SPSS Statistics 20.0 and were considered significant at p ≤ 0.05. Results: Knowledge of malaria symptoms, transmission, and prevention was reasonable among 55.8% (77) of the respondents. Only 33.6% (47) of the respondents could attribute the cause of malaria to protozoan of genus Plasmodium species. Of the 140 vendors, 115 (82.7%) prescribe antimalarial drugs. The knowledge of the national protocol was malaria case management among dispensers was 35.0%. Vendors in hospital/community pharmacies were 2.4 times (OR = 3.14, 95% CI: 4.14 - 8.74, p < 0.001) more knowledgeable about malaria treatment protocol than those of in drugstores. The prevalence of self-prescription of antimalarials was 39.3%. Self-prescription was significantly higher in drugstores than hospital/community pharmacies (p=0.004). In all, 56 (40.6%) of vendors showed good practices regarding antimalarial drug dispensing with the majority (51.7%) from community pharmacies (OR=2.27,95% CI: 1.13-4.56). Conclusion: Findings reveal moderate knowledge of malaria but poor prescription and dispensing practices of antimalarial drugs among vendors, thus indicating a need for routine monitoring and evaluation to prevent the emergence of resistant strains to current efficacious antimalarials.

Keywords: antimalarials, drug retail outlets, dispensing, drug resistance, prescription

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Authors: Venkata Srikanth Meka, Nur Arthirah Binti Ahmad Tarmizi Tan, Muhammad Syahmi Bin Md Nazir, Adinarayana Gorajana, Senthil Rajan Dharmalingam

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Biphasic drug delivery systems are designed to release drug at two different rates, either fast/prolonged or prolonged/fast. A fast/prolonged release system provides a burst drug release at initial stage followed by a slow release over a prolonged period of time and in case of prolonged/fast release system, the release pattern is vice versa. Terminalia catappa gum (TCG) is a natural polymer and was successfully proven as a novel pharmaceutical excipient. The main objective of the present research is to investigate the applicability of natural polymer, Terminalia catappa gum in the design of oral biphasic drug delivery system in the form of mini tablets by using a model drug, buspirone HCl. This investigation aims to produce a biphasic release drug delivery system of buspirone by combining immediate release and prolonged release mini tablets into a capsule. For immediate release mini tablets, a dose of 4.5 mg buspirone was prepared by varying the concentration of superdisintegrant; crospovidone. On the other hand, prolonged release mini tablets were produced by using different concentrations of the natural polymer; TCG with a buspirone dose of 3mg. All mini tablets were characterized for weight variation, hardness, friability, disintegration, content uniformity and dissolution studies. The optimized formulations of immediate and prolonged release mini tablets were finally combined in a capsule and was evaluated for release studies. FTIR and DSC studies were conducted to study the drug-polymer interaction. All formulations of immediate release and prolonged release mini tablets were passed all the in-process quality control tests according to US Pharmacopoeia. The disintegration time of immediate release mini tablets of different formulations was varied from 2-6 min, and maximum drug release was achieved in lesser than 60 min. Whereas prolonged release mini tablets made with TCG have shown good drug retarding properties. Formulations were controlled for about 4-10 hrs with varying concentration of TCG. As the concentration of TCG increased, the drug release retarding property also increased. The optimised mini tablets were packed in capsules and were evaluated for the release mechanism. The capsule dosage form has clearly exhibited the biphasic release of buspirone, indicating that TCG is a suitable natural polymer for this study. FTIR and DSC studies proved that there was no interaction between the drug and polymer. Based on the above positive results, it can be concluded that TCG is a suitable polymer for the biphasic drug delivery systems.

Keywords: Terminalia catappa gum, biphasic release, mini tablets, tablet in capsule, natural polymers

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Authors: Sharjeel Abid, Tanveer Hussain, Ahsan Nazir, Abdul Zahir, Nabyl Khenoussi

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Localized application of drug has various advantages and fewer side effects as compared with other methods. Burn patients suffer from swear pain and the major aspects that are considered for burn victims include pain and infection management. Nano-fibers (NFs) loaded with drug, applied on local wound area, can solve these problems. Therefore, this study dealt with the fabrication of drug loaded NFs for better pain management. Two layers of NFs were fabricated with different drugs. Contact layer was loaded with Gabapentin (a nerve painkiller) and the second layer with acetaminophen. The fabricated dressing was characterized using scanning electron microscope, Fourier Transform Infrared Spectroscopy, X-Ray Diffraction and UV-Vis Spectroscopy. The double layered based NFs dressing was designed to have both initial burst release followed by slow release to cope with pain for two days. The fabricated nanofibers showed diameter < 300 nm. The liquid absorption capacity of the NFs was also checked to deal with the exudate. The fabricated double layered dressing with dual drug loading and release showed promising results that could be used for dealing pain in burn victims. It was observed that by the addition of drug, the size of nanofibers was reduced, on the other hand, the crystallinity %age was increased, and liquid absorption decreased. The combination of fast nerve pain killer release followed by slow release of non-steroidal anti-inflammatory drug could be a good tool to reduce pain in a more secure manner with fewer side effects.

Keywords: pain management, burn wounds, nano-fibers, controlled drug release

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Authors: N. Maksimentseva

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The issue of public administration in subsoil use, renewal and protection is of high importance for Ukraine since it is strongly linked to energy security of the state as well as it shall facilitate the people of Ukraine to efficiently implement its propitiatory rights towards natural resources and redistribution of national wealth. As it is stipulated in the Article 11 of the Subsoil Code of Ukraine (the Code) the authorities that administer the industry are limited to central executive bodies and local governments. In particular, it is stipulated in the Code that the Ukraine’s Cabinet of Ministers carries out public administration in geological exploration, production and protection of subsoil. Other state bodies of public administration include central public authority responsible for state environmental protection policies; central public authority in charge of implementation of state geological exploration and efficient subsoil use policies; central authority in charge of state health and safety control policies. There are also public authorities in the Autonomous Republic of Crimea; local executive bodies and other state authorities and local self-government authorities in compliance with laws of Ukraine. This article is devoted to the analysis of the legal relations in the area of public administration of subsoil use, renewal and protection in Ukraine. The main approaches to study the essence of legal relations in the named area as well as its tasks, functions and methods are analyzed. It is concluded in this article that legal relationship in the field of public administration of subsoil use, renewal and protection is characterized by specifics of its task (development of natural resources).

Keywords: legal relations, public administration, subsoil code of Ukraine, subsoil use, renewal and protection

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Authors: Rashi Rajput, Manisha Singh

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Escitalopram oxalate (ETP), an FDA approved antidepressant drug from the category of SSRI (selective serotonin reuptake inhibitor) and is used in treatment of general anxiety disorder (GAD), major depressive disorder (MDD).When taken orally, it is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT) in the liver with the help of enzymes CYP2C19, CYP3A4 and CYP2D6. Hence, causing side effects such as dizziness, fast or irregular heartbeat, headache, nausea etc. Therefore, targeted and sustained drug delivery will be a helpful tool for increasing its efficacy and reducing side effects. The present study is designed for formulating mucoadhesive nanoparticle formulation for the same Escitalopram loaded polymeric nanoparticles were prepared by ionic gelation method and characterization of the optimised formulation was done by zeta average particle size (93.63nm), zeta potential (-1.89mV), TEM (range of 60nm to 115nm) analysis also confirms nanometric size range of the drug loaded nanoparticles along with polydispersibility index of 0.117. In this research, we have studied the in vitro drug release profile for ETP nanoparticles, through a semi permeable dialysis membrane. The three important characteristics affecting the drug release behaviour were – particle size, ionic strength and morphology of the optimised nanoparticles. The data showed that on increasing the particle size of the drug loaded nanoparticles, the initial burst was reduced which was comparatively higher in drug. Whereas, the formulation with 1mg/ml chitosan in 1.5mg/ml tripolyphosphate solution showed steady release over the entire period of drug release. Then this data was further validated through mathematical modelling to establish the mechanism of drug release kinetics, which showed a typical linear diffusion profile in optimised ETP loaded nanoparticles.

Keywords: ionic gelation, mucoadhesive nanoparticle, semi-permeable dialysis membrane, zeta potential

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Authors: Jichan Jang

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Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. In this study, we screened the library to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indication of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Thus, we found that compound X, identified, may be a promising candidate in the M. abscessus drug discovery pipeline.

Keywords: Mycobacterium abscessus, antibiotics, drug discovery, emerging Pathogen

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Authors: Anoosh Eghdami

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Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

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Authors: Ibrahim Abdulla Labib, Medhat Mohamed Morsy, Gamal Hosny, Hanan Dawood Yassa, Gaber Hassan

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Amiodarone is a very effective drug, widely used for arrhythmia. Unfortunately it has many side effects involving many organs especially thyroid gland. The current work was conducted to elucidate the effect of amiodarone on the thyroid gland and the possible protective role of vitamin E. Fifty adult male albino rats weighed 200 – 250 grams were divided into five groups; ten rats each. Group I (Control): Five rats were sacrificed after three weeks and five rats were sacrificed after six weeks. Group II (Sham control): Each rat received sunflower oil orally; the solvent of vitamin E for three weeks. Group III (Amiodarone-treated): each rat received an oral dose of amiodarone; 150 mg/kg/day for three weeks. Group IV (Recovery): Each rat received amiodarone as group III then the drug was stopped for three weeks to evaluate recovery. Group V (Amiodarone + Vitamin E-treated): Each rat received amiodarone as group III followed by 100 mg/kg/day vitamin E orally for three weeks. Thyroid gland of the sacrificed animals were dissected out and prepared for light and electron microscopic studies. Amiodarone administration resulted in loss of normal follicular architecture as many follicles appeared either shrunken, empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells while others showed interruption of their membrane. Masson's Trichrome stained sections showed increased collagen fibers in between the thyroid follicles. Ultrastructurally, the apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular with chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum with numerous lysosomes. After three weeks of stopping amiodarone, the follicles were nearly regular in outline. Some follicles were filled with homogenous eosinophilic colloid and others had shrunken pale colloid or were empty. Some few follicles showed exfoliated cells in their lumina and others were still lined by more than one layer of follicular cells. Moderate amounts of collagen fibers were observed in-between thyroid follicles. Ultrastructurally, many follicular cells had rounded euchromatic nucleui, moderate number of lysosomes and moderately dilated rough endoplasmic reticulum. However, few follicular cells still showing irregular nucleui, dilated rough endoplasmic reticulum and many cytoplasmic vacuoles. Administration of vitamin E with amiodarone for three weeks resulted in obvious structural improvement. Most of the follicles were lined by a single layer of cuboidal cells and the lumina were filled with homogenous eosinophilic colloid with very few vacuolations. The majority of follicular cells had rounded nuclei with occasional detection of ballooned cells and dark nuclei. Scanty collagen fibers were detected among thyroid follicles. Ultrastructurally, most follicular cells exhibited rounded euchromatic nuclei with few short microvilli were projecting into the colloid. Few lysosomes were also noticed. It was concluded that amiodarone administration leads to many adverse histological changes in the thyroid gland. Some of these changes are reversible during the recovery period however concomitant vitamin E administration with amiodarone has a major protective role in preventing many of these changes.

Keywords: amiodarone, recovery, ultrastructure, vitamin E.

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Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi

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Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.

Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths

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Authors: Umairah Natasya Binti Mohd Omeershffudin, Suresh Kumar

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Klebsiella pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. Particular concern is the global emergence of multidrug-resistant (MDR) strains of Klebsiella pneumoniae. Characterization of antibiotic resistance determinants at the genomic level plays a critical role in understanding, and potentially controlling, the spread of multidrug-resistant (MDR) pathogens. In this study, drug-resistant Klebsiella pneumoniae strain 825795-1 was investigated with extensive computational approaches aimed at identifying novel drug targets among hypothetical proteins. We have analyzed 1099 hypothetical proteins available in genome. We have used in-silico genome subtraction methodology to design potential and pathogen-specific drug targets against Klebsiella pneumoniae. We employed bioinformatics tools to subtract the strain-specific paralogous and host-specific homologous sequences from the bacterial proteome. The sorted 645 proteins were further refined to identify the essential genes in the pathogenic bacterium using the database of essential genes (DEG). We found 135 unique essential proteins in the target proteome that could be utilized as novel targets to design newer drugs. Further, we identified 49 cytoplasmic protein as potential drug targets through sub-cellular localization prediction. Further, we investigated these proteins in the DrugBank databases, and 11 of the unique essential proteins showed druggability according to the FDA approved drug bank databases with diverse broad-spectrum property. The results of this study will facilitate discovery of new drugs against Klebsiella pneumoniae.

Keywords: pneumonia, drug target, hypothetical protein, subtractive genomics

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Authors: Umme Hani, Mohammed Rahmatulla, Mohammed Ghazwani, Ali Alqahtani, Yahya Alhamhoom

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Background and introduction: Neratinib is a potent anticancer drug used for the treatment of breast cancer. It is poorly soluble at higher pH, which tends to minimize the therapeutic effects in the lower gastrointestinal tract (GIT) leading to poor bioavailability. An attempt has been made to prepare and develop a gastro-retentive system of Neratinib to improve the drug bioavailability in the GIT by enhancing the gastric retention time. Materials and methods: In the present study a three-factor at two-level (23) factorial design based optimization was used to inspect the effects of three independent variables (factors) such as sodium alginate (A), sodium bicarbonate (B) and sodium citrate (C) on the dependent variables like in vitro gelation, in vitro floating, water uptake and percentage drug release. Results: All the formulations showed pH in the range 6.7 ±0.25 to 7.4 ±0.24, percentage drug content was observed to be 96.3±0.27 to 99.5 ±0.28%, in vitro gelation observed as gelation immediate remains for an extended period. Percentage of water uptake was in the range between 9.01±0.15 to 31.01±0.25%, floating lag time was estimated form 7±0.39 to 57±0.36 sec. F4 and F5 showed floating even after 12hrs. All formulations showed a release of around 90% drug release within 12hr. It was observed that the selected independent variables affect the dependent variables. Conclusion: The developed system may be a promising and alternative approach to augment gastric retention of drugs and enhances the therapeutic efficacy of the drug.

Keywords: neratinib, 2³ factorial design, sodium alginate, floating, in situ gelling system

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Authors: Dmitry Nosik, Nickolay Nosik, Elli Kaplina, Olga Lobach, Marina Chataeva, Lev Rasnetsov

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Background and aims: Human Immunodeficiency Virus (HIV) infection is very often associated with Herpes Simplex Virus (HSV) infection but HIV patients are treated with a cocktail of antiretroviral drugs which are toxic. The use of an antiviral drug which will be active against both viruses like ferrovir found in our previous studies is rather actual. Earlier we had shown that Fullerene poly-amino capronic acid (FPACA) was active in case of monoinfection of HIV-1 or HSV-1. The aim of the study was to analyze the efficiency of FPACA against mixed infection of HIV and HSV. Methods: The peripheral blood lymphocytes, CEM, MT-4 cells were simultaneously infected with HIV-1 and HSV-1. FPACA was added 1 hour before infection. Cells viability was detected by MTT assay, virus antigens detected by ELISA, syncytium formation detected by microscopy. The different multiplicity of HIV-1/HSV-1 ratio was used. Results: The double viral HIV-1/HSV-1 infection was more cytopathic comparing with monoinfections. In mixed infection by the HIV-1/HSV-1 concentration of HIV-1 antigens and syncytium formations increased by 1,7 to 2,3 times in different cells in comparison with the culture infected with HIV-1 alone. The concentration of HSV-1 increased by 1,5-1,7 times, respectively. Administration of FPACA (1 microg/ml) protected cells: HIV-1/HSV-1 (1:1) – 80,1%; HIV-1/HSV-1 (1:4) – 57,2%; HIV-1/HSV-1 (1:8) – 46,3 %; HIV-1/HSV-1 (1:16) – 17,0%. Virus’s antigen levels were also reduced. Syncytium formation was totally inhibited in all cases of mixed infection. Conclusion: FPACA showed antiviral activity in case of mixed viral infection induced by Human Immunodeficiency Virus and Herpes Simplex Virus. The effect of viral inhibition increased with the multiplicity of HIV-1 in the inoculum. The mechanism of FPACA action is connected with the blocking of the virus particles adsorption to the cells and it could be suggested that it can have an antiviral activity against some other viruses too. Now FPACA could be considered as a potential drug for treatment of HIV disease complicated with opportunistic herpes viral infection.

Keywords: antiviral drug, human immunodeficiency virus (hiv), herpes simplex virus (hsv), mixed viral infection

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Authors: M. Kumpugdee-Vollrath, J.-P. Krause, S. Bürk

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Most of the drugs used for pharmaceutical purposes are poorly water-soluble drugs. About 40% of all newly discovered drugs are lipophilic and the numbers of lipophilic drugs seem to increase more and more. Drug delivery systems such as nanoparticles, micelles or liposomes are applied to improve their solubility and thus their bioavailability. Besides various techniques of solubilization, oil-in-water emulsions are often used to incorporate lipophilic drugs into the oil phase. To stabilize emulsions surface active substances (surfactants) are generally used. An alternative method to avoid the application of surfactants was of great interest. One possibility is to develop O/W-emulsion without any addition of surface active agents or the so called “surfactant-free emulsion or SFE”. The aim of this study was to develop and characterize SFE as a drug carrier by varying the production conditions. Lidocaine base was used as a model drug. The injection method was developed. Effects of ultrasound as well as of temperature on the properties of the emulsion were studied. Particle sizes and release were determined. The long-term stability up to 30 days was performed. The results showed that the surfactant-free O/W emulsions with pharmaceutical oil as drug carrier can be produced.

Keywords: emulsion, lidocaine, Miglyol, size, surfactant, light scattering, release, injection, ultrasound, stability

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Authors: Naima Nur, Safa Islam, Saeema Islam, Faridul Alam

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Background: Drug-resistant pulmonary tuberculosis (DR-PTB), particularly multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant (pre-XDR), is a major challenge in effectively controlling TB, especially in developing. This study aimed to identify the strains of M. tuberculosis complex (MTC) and drug resistance patterns among the pulmonary tuberculosis patients. Methods: The study used a cross-sectional design, and 815 patients were recruited randomly in three study periods. In the first-period, 210 treated PTB patients, who were completed their treatment, received their diagnoses using light microscopy, fluorescence microscopy and cultured on Lowenstein-Jensen (L-J) slant, and then strains were identified as MTC by biochemical tests, and then sensitivity test in National Institute of Diseases of the Chest and Hospital. In the second-period, 220 re-treated PTB patients, who were completed their treatment, received their diagnoses using culture on L-J slant, line probe assay (LPA), and GeneXpert in the same hospital. In the last-period, during treatment, 385 MDR-PTB patients received their diagnoses using culture on L-J slant and LPA in the same hospital. Results: Among sixty-two (29.5%) PTB patients, 13% were sensitive to all first-line anti-TB drugs, 26% were MDR-TB patients, and 14.2% were pre-XDR-TB among 14 MDR-TB patients. After three years, 31% were MDR-TB among 220 re-treated PTB patients. After five years, 16.4% was pre-XDR-TB among 385 MDR-TB patients. Compared to females, male patients were significantly higher at all times. Conclusion: The current study demonstrated that in three study periods, the proportions of DR-TB, MDR-TB, and pre-XDR patients were an alarming issue and increasing daily.

Keywords: multi-drug resistant, drug-resistant, pre-extensive drug resistant, pulmonary tuberculosis

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Authors: Courtney Evans, Yuto Morimitsu, Tsubasa Hisadome, Futo Inomoto, Masahiro Yoshida, Takayuki Takei

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Hydrogels are useful biomaterials due to their highly biocompatible nature and their ability to absorb large quantities of liquid and mimic soft tissue. They are often used as therapeutic drug delivery systems. However, it is sometimes difficult to sustain controlled release when using hydrophobic medicines, as hydrogels are frequently hydrophilic. As such, this research shows the success of chitosan hydrogels modified through hydrophobic interaction. This was done through the imide bonding of the alkyl groups in fatty aldehydes and the amino groups in chitosan, followed by reductive animation. The resulting cryogels could be optimized for strength as well as sorption and desorption (of a hydrophobic dye used to mimic hydrophobic medicine) by varying the alkyl chain length and the substitution degree of the fatty aldehyde. Optimized cryogels showed potential as biomedical materials, particularly as drug delivery systems.

Keywords: biomedical materials, chitosan, drug carriers, hydrophobic modification

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Authors: Sukanya Sripho

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The purpose of this research was to study the role of local administration management to promote culture based on philosophy of sufficiency economy to many communities in Thailand. The philosophy was given to the Thai people by their King and become one of the important policies from the Thai government. A total of 375 local people in main district, Amnadcharoen province were selected by random sampling. A questionnaire was used as the tool for collecting data. Descriptive statistics in this research included percentage, mean, and multiple regression analysis. The findings revealed that the role of facilitator was utilized the most from the management in order to promote culture based on philosophy of sufficiency economy to many communities in Thailand.

Keywords: administration, management, philosophy of sufficiency economy, facilitator

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Authors: Kheireddine El-Boubbou

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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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Authors: Nirupama Dixit, Anyaa Mittal, Neeru Sood

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Alzheimer’s disease (AD) is a progressive form of dementia, contributing to up to 70% of cases, mostly observed in elderly but is not restricted to old age. The pathophysiology of the disease is characterized by specific pathological changes in brain. The changes (i.e. accumulation of metal ions in brain, formation of extracellular β-amyloid (Aβ) peptide aggregates and tangle of hyper phosphorylated Tau protein inside neurons) damage the neuronal connections irreversibly. The current issues in improvement of life quality of Alzheimer's patient lies in the fact that the diagnosis is made at a late stage of the disease and the medications do not treat the basic causes of Alzheimer's. The targeted delivery of drug through the blood brain barrier (BBB) poses several limitations via traditional approaches for treatment. To overcome these drug delivery limitation, nanoparticles provide a promising solution. This review focuses on current strategies for efficient targeted drug delivery using nanoparticles and improving the quality of therapy provided to the patient. Nanoparticles can be used to encapsulate drug (which is generally hydrophobic) to ensure its passage to brain; they can be conjugated to metal ion chelators to reduce the metal load in neural tissue thus lowering the harmful effects of oxidative damage; can be conjugated with drug and monoclonal antibodies against BBB endogenous receptors. Finally this review covers how the nanoparticles can play a role in diagnosing the disease.

Keywords: Alzheimer's disease, β-amyloid plaques, blood brain barrier, metal chelators, nanoparticles

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Ashley R. Logsdon, Becky F. Antle, Cynthia M. Kamer

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This study examines the cost and benefits of a family treatment drug court in an urban county in a southeastern state. Additionally, this cost analysis will provide a detailed description of the type and cost of activities to produce the services provided to child welfare families. This study utilized return-on-investment analysis, which uses child welfare practices, disaggregates them into separate activities and estimates costs for these activities including child-level placement data for total cost of care for the child. Direct and indirect costs were considered as well as saving calculations what costs would be associated with child welfare outcomes both short and long term. The costs included were general program costs (salaries, drug screens, transportation, childcare, parent education, program evaluation, visitation, incentives) or personnel costs for other team members (judges, court administrators, child welfare workers, child welfare supervisors, and community mental health provider). The savings that were used in the study were length of time in out of home care, Medicaid costs, substance exposed births, emergency room utilization and jail/probation costs. This study documents an overall savings of between $168,993.30 and $837,993.30. The total savings per family divided by the 40 families who have participated in the program was between $4,224.83 to $20,949.83 per family. The results of this cost benefit analysis are consistent with prior research documenting savings associated with out of home care and jail/probation; however, there are also unique contributions of this study to the literature on cost effectiveness of family treatment drug courts. We will present recommendations for further utilization of family treatment drug courts and how to expand the current model.

Keywords: child welfare, cost analysis, family drug court, family treatment drug court

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Authors: Thippharat Wongsilarat, Parichat tuntilanon, Chonlakan Prataksitorn

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Recurrent adverse drug reactions are harmful to patients with mild to fatal illnesses, and affect not only patients but also their relatives, and organizations. To compare safe use of medicine among patients before and after using the recurrent adverse drug reaction prevention program . Quasi-experimental research with the target population of 598 patients with drug allergy history. Data were collected through an observation form tested for its validity by three experts (IOC = 0.87), and analyzed with a descriptive statistic (percentage). The research was conducted jointly with a multidisciplinary team to analyze and determine the weak points and strong points in the recurrent adverse drug reaction prevention system during the past three years, and 546, 329, and 498 incidences, respectively, were found. Of these, 379, 279, and 302 incidences, or 69.4; 84.80; and 60.64 percent of the patients with drug allergy history, respectively, were found to have caused by incomplete warning system. In addition, differences in practice in caring for patients with drug allergy history were found that did not cover all the steps of the patient care process, especially a lack of repeated checking, and a lack of communication between the multidisciplinary team members. Therefore, the recurrent adverse drug reaction prevention program was developed with complete warning points in the information technology system, the repeated checking step, and communication among related multidisciplinary team members starting from the hospital identity card room, patient history recording officers, nurses, physicians who prescribe the drugs, and pharmacists. Including in the system were surveillance, nursing, recording, and linking the data to referring units. There were also training concerning adverse drug reactions by pharmacists, monthly meetings to explain the process to practice personnel, creating safety culture, random checking of practice, motivational encouragement, supervising, controlling, following up, and evaluating the practice. The rate of prescribing drugs to which patients were allergic per 1,000 prescriptions was 0.08, and the incidence rate of recurrent drug reaction per 1,000 prescriptions was 0. Surveillance of recurrent adverse drug reactions covering all service providing points can ensure safe use of medicine for patients.

Keywords: recurrent drug, adverse reaction, safety, use of medicine

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Authors: M. S. Deshpande, Snehal D. Bomble

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Tuberculosis (TB) is a deadly contagious disease that is caused by a bacterium called Mycobacterium tuberculosis. More than sixty years ago, the introduction of the first anti-TB drugs for the treatment of TB (streptomycin (STR), p-aminosalcylic acid (PAS), isoniazid (INH), and then later ethambutol (EMB) and rifampicin (RIF)) gave optimism to the medical community, and it was believed that the disease would be completely eradicated soon. Worldwide, the number of TB cases has continued to increase, but the incidence rate has decreased since 2003. Recently, highly drug-resistant forms of TB have emerged worldwide. The prolonged use of classical drugs developed a growing resistance and these drugs have gradually become less effective and incapable to meet the challenges, especially those of multi drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB, and HIV-TB co-infections. There is an unmet medical need to discover newer synthetic molecules and new generation of potent drugs for the treatment of tuberculosis which will shorten the time of treatment, be potent and safe while effective facing resistant strains and non-replicative, latent forms, reduce adverse side effect and not interfere in the antiretroviral therapy. This paper attempts to bring out the review of anti-TB drugs, and presents a novel method of synthesizing new anti-tuberculosis drugs and potential compounds to overcome the bacterial resistance and combat the re-emergence of tuberculosis.

Keywords: tuberculosis, mycobacterium, multi-drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB

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Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

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New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

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Authors: Prakash Singh

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Schools throughout the world are facing increasing challenges in dealing with school violence and drug abuse by pupils. Therefore, the question of the fear of failure to meet the aims and objectives of education inevitably surfaces as it places increasing and challenging demands on educators and all other stakeholders to address this malaise. Multiple studies on the construct tobephobia (TBP) simply define TBP as the fear of failure in education. This study is a continuation of the exploratory studies on the manifestation of fear in education. The primary purpose of this study was to establish how TBP, caused by school violence and drug abuse affects teaching and learning in our schools. The qualitative research method was used for this study. Teachers admitted that they fear for their safety at school. Working in a fearful situation places a high rate of stress and anxiety on them. Tobephobic educators spend most of their time worrying about their fear of violence and drug abuse by pupils and are too frightened to carry out their normal duties. They prefer to stay in familiar surroundings for fear of being attacked by inebriated learners. This study, therefore, contributes to our understanding of the effects of TBP in our schools caused by school violence and drug abuse. Also, this study supplements the evidence accumulated over the past fifteen years that TBP is not a figment of someone’s imagination; it is a gruesome reality affecting the very foundation of our educational system globally to provide quality and equal education to all our learners in a harmonious, collegial school environment.

Keywords: tobephobia, tobephobic educators, fear of failure in education, school violence, drug abuse

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Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

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Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

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Authors: Auni Idi Muhire

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Background: Prior to April 2012, resuscitations were often ineffective resulting in poor patient outcomes. An initiative was implemented at Rwanda Military Hospital (RMH) to review root causes and plan strategies to improve patient outcomes. An interdisciplinary committee was developed to review this problem. Purpose: Analyze the frequency, obstacles, and outcome of patient resuscitation following cardiac and/or respiratory arrest. Methods: A form was developed to allow recording of all actions taken during resuscitation including response times, staff present, and equipment and medications used. Results:-The patient population requiring the most resuscitation effort are the intensive care patients, most frequently the neonatal the intensive care patients (42.8%) -Despite having trained staff representatives, not all resuscitations follow protocol -Lack of compliance with drug administration guidelines was noted, particularly in initiating use of drugs despite the drug being available (59%). Lesson Learned: Basic Life Support training for interdisciplinary staff resulted in more effective response to cardiac and/or respiratory arrest at RMH. Obstacles to effective resuscitation included number of staff, knowledge and skill level of staff, availability of appropriate equipment and medications, staff communication, and patient Do not Attempt Resuscitation (DNR) status.

Keywords: resuscitation, case analysis of knowledge versus practice, intensive care, critical care

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Authors: Maryam Vaezjalali, Koroush Rahimian, Maryam Asli, Tahmineh Kandelouei, Foad Davoodbeglou, Amir H. Kashi

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Objectives: The present study was conducted to assess the HBV molecular profiles including genotypes, subgenotypes, subtypes & mutations in hepatitis B genes. Materials/Patients and Methods: This study was conducted on 229 intravenous drug users who referred to three Drop- in-Centers and a hospital in Tehran. HBV DNA was extracted from HBsAg positive serum samples and amplified by Nested PCR. HBV genotype, subgenotypes, subtype and genes mutation were determined by direct sequencing. Phylogenetic tree was constructed using neighbor- joining (NJ) method. Statistical analyses were carried out by SPSS 20. Results: HBV DNA was found in 3 HBsAg positive cases. Phylogenetic tree of derived HBV DNAs showed the existence of genotype D (subgenotype D1, subtype ayw2). Also immune escape mutations were determined in S gene. Conclusion: There were a few variations and genotypes and subtypes among infected intravenous drug users. This study showed the predominance of genotype D among intravenous drug users. Our study concurs with other reports from Iran, that all showing currently only genotype D is the only detectable genotype in Iran.

Keywords: drug users, genotype, HBV, phylogenetic tree

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Authors: Ragaa T. Darwish, Maha A. Demellawy, Haidy M. Megahed, Doreen N. Younan, Wael S. Kholeif

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The testing of drug abuse is authentic in order to affirm the misuse of drugs. Several analytical approaches have been developed for the detection of drugs of abuse in pharmaceutical and common biological samples, but few methodologies have been created to identify them from fingerprints. Liquid Chromatography-Mass Spectrometry (LC-MS) plays a major role in this field. The current study aimed at assessing the possibility of detection of some drugs of abuse (tramadol, clonazepam, and phenobarbital) from fingerprints using LC-MS in drug abusers. The aim was extended in order to assess the possibility of detection of the above-mentioned drugs in fingerprints of drug handlers till three days of handling the drugs. The study was conducted on randomly selected adult individuals who were either drug abusers seeking treatment at centers of drug dependence in Alexandria, Egypt or normal volunteers who were asked to handle the different studied drugs (drug handlers). An informed consent was obtained from all individuals. Participants were classified into 3 groups; control group that consisted of 50 normal individuals (neither abusing nor handling drugs), drug abuser group that consisted of 30 individuals who abused tramadol, clonazepam or phenobarbital (10 individuals for each drug) and drug handler group that consisted of 50 individuals who were touching either the powder of drugs of abuse: tramadol, clonazepam or phenobarbital (10 individuals for each drug) or the powder of the control substances which were of similar appearance (white powder) and that might be used in the adulteration of drugs of abuse: acetyl salicylic acid and acetaminophen (10 individuals for each drug). Samples were taken from the handler individuals for three consecutive days for the same individual. The diagnosis of drug abusers was based on the current Diagnostic and Statistical Manual of Mental disorders (DSM-V) and urine screening tests using immunoassay technique. Preliminary drug screening tests of urine samples were also done for drug handlers and the control groups to indicate the presence or absence of the studied drugs of abuse. Fingerprints of all participants were then taken on a filter paper previously soaked with methanol to be analyzed by LC-MS using SCIEX Triple Quad or QTRAP 5500 System. The concentration of drugs in each sample was calculated using the regression equations between concentration in ng/ml and peak area of each reference standard. All fingerprint samples from drug abusers showed positive results with LC-MS for the tested drugs, while all samples from the control individuals showed negative results. A significant difference was noted between the concentration of the drugs and the duration of abuse. Tramadol, clonazepam, and phenobarbital were also successfully detected from fingerprints of drug handlers till 3 days of handling the drugs. The mean concentration of the chosen drugs of abuse among the handlers group decreased when the days of samples intake increased.

Keywords: drugs of abuse, fingerprints, liquid chromatography–mass spectrometry, tramadol

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