Search results for: antiplatelet drugs

Authors: Pompa Marcello, Mauro Capocelli, Vincenzo Piemonte

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This work focuses on a mathematical model able to describe the gastro-intestinal physiology and providing a rational tool for the design of an artificial gastro-intestinal system. This latter is mainly devoted to analyse the absorption and bioavailability of drugs and nutrients through in vitro tests in order to overcome (or, at least, to partially replace) in vivo trials. The provided model realizes a conjunction ring (with extended prediction capability) between in vivo tests and mechanical-laboratory models emulating the human body. On this basis, no empirical equations controlling the gastric emptying are implemented in this model as frequent in the cited literature and all the sub-unit and the related system of equations are physiologically based. More in detail, the model structure consists of six compartments (stomach, duodenum, jejunum, ileum, colon and blood) interconnected through pipes and valves. Paracetamol, Ketoprofen, Irbesartan and Ketoconazole are considered and analysed in this work as reference drugs. The mathematical model has been validated against in vivo literature data. Results obtained show a very good model reliability and highlight the possibility to realize tailored simulations for different couples patient-drug, including food adsorption dynamics.

Keywords: gastro-intestinal model, drugs bioavailability, paracetamol, ketoprofen

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Mustafa Al Sukar, Azzam Sleit, Abdullatif Abu-Dalhoum, Bassam Al-Kasasbeh

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Use and abuse of drugs by teens is very common and can have dangerous consequences. The drugs contribute to physical and sexual aggression such as assault or rape. Some teenagers regularly use drugs to compensate for depression, anxiety or a lack of positive social skills. Teen resort to smoking should not be minimized because it can be "gateway drugs" for other drugs (marijuana, cocaine, hallucinogens, inhalants, and heroin). The combination of teenagers' curiosity, risk taking behavior, and social pressure make it very difficult to say no. This leads most teenagers to the questions: "Will it hurt to try once?" Nowadays, technological advances are changing our lives very rapidly and adding a lot of technologies that help us to track the risk of drug abuse such as smart phones, Wireless Sensor Networks (WSNs), Internet of Things (IoT), etc. This technique may help us to early discovery of drug abuse in order to prevent an aggravation of the influence of drugs on the abuser. In this paper, we have developed a Decision Support System (DSS) for detecting the drug abuse using Artificial Neural Network (ANN); we used a Multilayer Perceptron (MLP) feed-forward neural network in developing the system. The input layer includes 50 variables while the output layer contains one neuron which indicates whether the person is a drug addict. An iterative process is used to determine the number of hidden layers and the number of neurons in each one. We used multiple experiment models that have been completed with Log-Sigmoid transfer function. Particularly, 10-fold cross validation schemes are used to access the generalization of the proposed system. The experiment results have obtained 98.42% classification accuracy for correct diagnosis in our system. The data had been taken from 184 cases in Jordan according to a set of questions compiled from Specialists, and data have been obtained through the families of drug abusers.

Keywords: drug addiction, artificial neural networks, multilayer perceptron (MLP), decision support system

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Authors: Abhay Vir Singh Kanwar

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The pharmaceutical industry today is a multi-billion dollar business and yet disadvantages people in many corners of the globe who are still dying in large numbers from curable illnesses for lack of access to drugs. The astronomical prices of essential and life-saving drugs is not just an economic problem that can be settled through clever market strategies but is an ethical issue, given the accumulated wealth of today’s humanity and the sense of global justice that it increasingly comes to share. In this paper, I make a very practical argument for what I shall call ‘the ethical healthcare paradigm’, which, I propose, can replace the economistic paradigm that can still drive the healthcare sector without creating spillover effects on the market. Taking off from the ethical-philosophical argument for recognizing every individual’s right to capability to be healthy, I shall come to the focused practical proposal of the cost-rationalization and universal availability of essential, life-saving drugs through the undertaking of research and development funding for drug innovation by the business establishment as such in terms of the concept of CSR. The paper will first expose the concepts of basic and fundamental capabilities in relation to education and health, after which it will focus on the right to capability to be healthy of every person. In the third section, it will discuss the ‘ethical healthcare paradigm’ as opposed to the economistic health paradigm and will argue that the patient will have to be considered the primary stakeholder of this paradigm or the very ‘subject’ of healthcare. The next section will be on an ethical-historical critique of the pharmaceutical industry’s profit driven economism. The section after that will look at the business operation and the stages in the life cycle of a drug that comes to the market in order to understand the risks, strengths and problems of the pharmaceutical industry. Finally, the paper will discuss the concept of CSR in relation to the ethical healthcare paradigm in order to propose CSR funding in research and development for innovation on drugs so that life-saving drugs can be made available to every sick person cost-effectively.

Keywords: capability approach, healthcare, CSR, patient

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Authors: Raj Kumar, Prem Felix Siril

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The poor aqueous solubility of many pharmaceutical drugs and potential drug candidates is a big challenge in drug development. Nanoformulation of such candidates is one of the major solutions for the delivery of such drugs. We initially developed the evaporation assisted solvent-antisolvent interaction (EASAI) method. EASAI method is use full to prepared nanoparticles of poor water soluble drugs with spherical morphology and particles size below 100 nm. However, to further improve the effect formulation to reduce number of dose and side effect it is important to control the delivery of drugs. However, many drug delivery systems are available. Among the many nano-drug carrier systems, solid lipid nanoparticles (SLNs) have many advantages over the others such as high biocompatibility, stability, non-toxicity and ability to achieve controlled release of drugs and drug targeting. SLNs can be administered through all existing routes due to high biocompatibility of lipids. SLNs are usually composed of lipid, surfactant and drug were encapsulated in lipid matrix. A number of non-steroidal anti-inflammatory drugs (NSAIDs) have poor bioavailability resulting from their poor aqueous solubility. In the present work, SLNs loaded with NSAIDs such as Nabumetone (NBT), Ketoprofen (KP) and Ibuprofen (IBP) were successfully prepared using different lipids and surfactants. We studied and optimized experimental parameters using a number of lipids, surfactants and NSAIDs. The effect of different experimental parameters such as lipid to surfactant ratio, volume of water, temperature, drug concentration and sonication time on the particles size of SLNs during the preparation using hot-melt sonication was studied. It was found that particles size was directly proportional to drug concentration and inversely proportional to surfactant concentration, volume of water added and temperature of water. SLNs prepared at optimized condition were characterized thoroughly by using different techniques such as dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). We successfully prepared the SLN of below 220 nm using different lipids and surfactants combination. The drugs KP, NBT and IBP showed 74%, 69% and 53% percentage of entrapment efficiency with drug loading of 2%, 7% and 6% respectively in SLNs of Campul GMS 50K and Gelucire 50/13. In-vitro drug release profile of drug loaded SLNs is shown that nearly 100% of drug was release in 6 h.

Keywords: nanoparticles, delivery, solid lipid nanoparticles, hot-melt sonication, poor water soluble drugs, solubility, bioavailability

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Authors: Rujnan Tuna, Ulku Baykal

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The antineoplastic drugs used in cancer treatment directly have adverse effects on health of both patients receiving the treatment and oncology nurses preparing and administering the treatment. The purpose of this study is to determine the working conditions of the oncology nurses in terms of employee safety as well as their knowledge levels regarding the safe use of antineoplastic drugs. This is a qualitative study conducted in the phenomenological design. Purposeful sampling method was used to carry out the interviews. The individual, in-depth, and semi-structured face-to-face interviews continued with 25 oncology nurses, who were working in an oncology centre in the city of Istanbul. Qualitative content analysis approach was used for the analysis of the obtained data in the study. The results of the study were gathered under 4 main themes; work-related factors, employee safety, working conditions, and training. The interviewed oncology nurses stated that the protective measures related to the safe use of the antineoplastic drugs were insufficient, and only 20% of the nurses have chemotherapy preparation certificate and they received this certificate after they started working in this unit. Also, after they had begun to work in that unit, they started to experience with so many health problems As happens all over the world, there have also been policies and standards regarding the safe use of antineoplastic drugs in Turkey; however, it is found that they remain insufficient to put into practice.

Keywords: antineoplastic drug, employee safety, nurse, oncology, qualitative study

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Authors: Hüseyin Biçer

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The purpose of this study is an explanation of using and expectation traditional and complementary medicine in Turkey in terms of regionally, cultural and social. Due to geopolitics position, at the intersection of the Middle East, Africa and Europe, Turkey has historically hosted many civilizations and cultures, and hosts many religions at the same time and therefore is very open to intercultural interaction. For this reason, the traditional medicine of Turkey contains traces of many civilizations rather than a traditional medicine of its own. In Turkey, complementary and traditional medicine are used actively. The aim of the study is to measure whether the patients have ever taken traditional medicine as a caretaker or for the supportive treatment of their diseases, and as a result, their expectations. This cross-sectional, paper-based survey study was conducted in 27 state hospitals and 29 family medicine clinics in seven geographical regions of Turkey. Patients who had an appointment in the waiting rooms that day were included. 77.4% of the patients participating in the study stated that they used traditional medicine at least 5 times in their life, 27.6% stated that traditional medicine was sufficient in some diseases, and 36.8% stated that traditional treatment was a part of normal treatment. Both faith and cultural approaches in Turkey always keep traditional medicine close to drugs. Another danger, apart from traditional medicine drugs that can interact with drugs, is that patients find it sufficient to use traditional and complementary medicine alone.

Keywords: complementary medicine, traditional medicine, medicine in Turkey, alternative medicine

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Authors: Abraham J. Domb

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Nearly every eye disorder and treatment of post operated eyes evolve around ocular drug delivery. Most ocular diseases are treated with repeated topical applications administered as eye drops. Various attempts have been made to improve drug bioavailability by increasing both the retention of the drug in the pre-corneal area and the penetration of the drug through the cornea. However, currently marketed products are associated with vision blurring, irritability, patient discomfort, toxicity, low drug bioavailability, manufacturing difficulties and inadequate aqueous stability. It has been suggested to use iontophoresis for the non-invasive delivery of drugs. The iontophoretic device is composed of a control panel, two electrodes, a cylindrical well for the insertion of a disposable hydrogel, and a disposable hydrogel pellet. The drug-loaded hydrogel is attached to a cylindrical well at the edge of the electrode of the device and placed onto the eye. The device applies a variable electrical current that can vary from 0.1 mA to 1.5 mA for pre-set periods from 10 seconds to 300 seconds. The iontophoretic device developed in the lab was found to be effective in the delivery of the drugs: gentamicin, water-soluble steroids, and various anticancer agents. When testing in rabbits for safety, the device was considered to be non-toxic and effective.

Keywords: iontophoresis, eye disorder, drug delivery, hydrogel

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Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Mohammed Albeishy, Mohammed A. Hakami, Farid M. Abualsail, Magbool Oraiby, Mohammed Alattas, Ali Muyidi, Ibraheem Attafi

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The current retrospective study's objective was to analyze the forensic toxicological findings of fatal suicide hangings that occurred in Jazan between 2018 and 2022. Methods: This study includes all forensic toxicology cases where the cause of death was hanging suicide. To establish the presence of drugs, postmortem samples were examined by forensic toxicology services. Results: The results showed that 132 cases of hanging fatalities out of 802 total cases were studied throughout the study period, with 86.4% of the fatalities being male, 13.6% being female, 33.3% Saudi, and 66.6% non-Saudi. The younger age group, between 18 and 29, was more prevalent. The Saudi population has seen an increase in the number of hanging fatalities each year. With an increase in hanging fatalities, the proportion of drug-related deaths by hanging slightly increased. Multiple drugs usage is the most prevalent drug use pattern among all age categories. Amphetamine was the most frequent drug presence in hanging cases who used one drug. Amphetamine and ethanol were the most frequent combination. Conclusion: In conclusion, hanging deaths were more common in young males, with majority of non-Saudi. Multiple drug use was the most common drug use pattern in hanging fatalities across all age categories, with amphetamine and ethanol predominant. More studies are required regarding the link between certain drugs and suicide by hanging. Preventive measures should be take these risk factors into consideration.

Keywords: forensic toxicology, suicides, hanging, amphetamine, ethanol

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Authors: Seyran Naghdi

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Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

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Authors: M. A. Ferhat, M. N. Boukhatem, F. Chemat

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Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 ml of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

Keywords: anti-inflammatory effect, carrageenan, citronellol, histopathology, Rose geranium

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Authors: Meenu Mehta, Munish Garg

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The use of oral anticancer drugs from AYUSH system of medicine is widely increased among the society due to their low cost, enhanced efficacy, increased patient preference, lack of inconveniences related to infusion and they provide an opportunity to develop chronic treatment regimens. However, oral delivery of these drugs usually laid down by the limited bioavailability of the drug, which is associated with a wide variation. As most of the cytotoxic agents have a narrow therapeutic window and are dosed at or near the maximum tolerated dose, a wide variability in the bioavailability can negatively affect treatment result. It is estimated that 40% of active substances are poorly soluble in water. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. There are several techniques reported in literature. Among all these Self Emulsifying Drug Delivery System (SEDDS) has gained more attention due to enhanced oral bio-availability enabling a reduction in dose. Thus, SEDDS anticancer drugs will have the increased bioavailability and efficacy. These dosage form will provide societal benefit in a cost-effective manner as compared to other oral dosage forms. Present study reflects on the formulation strategies as SEDDS for oral anticancer agents of AYUSH system for enhanced bioavailability with proven efficacy by cancer cell lines.

Keywords: anticancer agents, AYUSH system, bioavailability, SEDDS

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Authors: Rashini Maduka, C. R. Wijesinghe, A. R. Weerasinghe

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Drug-drug interactions (DDIs) can happen when two or more drugs are taken together. Today DDIs have become a serious health issue due to adverse drug effects. In vivo and in vitro methods for identifying DDIs are time-consuming and costly. Therefore, in-silico-based approaches are preferred in DDI identification. Most machine learning models for DDI prediction are used chemical and biological drug properties as features. However, some drug features are not available and costly to extract. Therefore, it is better to make automatic feature engineering. Furthermore, people who have diabetes already suffer from other diseases and take more than one medicine together. Then adverse drug effects may happen to diabetic patients and cause unpleasant reactions in the body. In this study, we present a model with a graph convolutional autoencoder and a graph decoder using a dataset from DrugBank version 5.1.3. The main objective of the model is to identify unknown interactions between antidiabetic drugs and the drugs taken by diabetic patients for other diseases. We considered automatic feature engineering and used Known DDIs only as the input for the model. Our model has achieved 0.86 in AUC and 0.86 in AP.

Keywords: drug-drug interaction prediction, graph embedding, graph convolutional networks, adverse drug effects

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Authors: Babak Bahri, Fatemeh Yassaee Meybodi, Changiz Eslahchi

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In the pursuit of effective cancer therapies, the exploration of combinatorial drug regimens is crucial to leverage synergistic interactions between drugs, thereby improving treatment efficacy and overcoming drug resistance. However, identifying synergistic drug pairs poses challenges due to the vast combinatorial space and limitations of experimental approaches. This study introduces ClusterSyn, a machine learning (ML)-powered framework for classifying anti-cancer drug synergy scores. ClusterSyn employs a two-step approach involving drug clustering and synergy score prediction using a fully connected deep neural network. For each cell line in the training dataset, a drug graph is constructed, with nodes representing drugs and edge weights denoting synergy scores between drug pairs. Drugs are clustered using the Markov clustering (MCL) algorithm, and vectors representing the similarity of drug pairs to each cluster are input into the deep neural network for synergy score prediction (synergy or antagonism). Clustering results demonstrate effective grouping of drugs based on synergy scores, aligning similar synergy profiles. Subsequently, neural network predictions and synergy scores of the two drugs on others within their clusters are used to predict the synergy score of the considered drug pair. This approach facilitates comparative analysis with clustering and regression-based methods, revealing the superior performance of ClusterSyn over state-of-the-art methods like DeepSynergy and DeepDDS on diverse datasets such as Oniel and Almanac. The results highlight the remarkable potential of ClusterSyn as a versatile tool for predicting anti-cancer drug synergy scores.

Keywords: drug synergy, clustering, prediction, machine learning., deep learning

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Authors: Gian Marco Di Feo

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Purpose: The study was conducted to examine changes in the beliefs and contents of articles on autism since the mid-twentieth century. Characteristics analyzed were the mentioning of pharmaceutical drugs, country, and institution of the first author, methodologies used, journal, and the year of publication. Methods: All articles (N=566) analyzed were published between January 1st, 1943 and December 31st, 2021. Inter rater reliability was assessed and there was a 94.4 percent agreement amongst raters. All articles were analyzed through both PubMed and PsycInfo. Results: A one way chi square indicated that there was a significant number of articles expressing mixed beliefs on the cause of autism. Scientific perspectives on the cause of autism have changed significantly over time. Particularly, the belief of empiricism (environmental factors) has decreased significantly, while both mixed beliefs and nativism have increased remarkably. Additionally, the mentioning of pharmaceutical drugs is involved with the beliefs on the cause of autism. Conclusion: Articles in the twenty first century are most likely to express both nativist and empiricist viewpoints on the cause of autism. Articles that express mixed beliefs are most likely to mention drugs in their study. The results impact scientific self-understanding on autism and beliefs in high-income countries, and advance scientific understanding globally.

Keywords: autism, beliefs, nativism, empiricism, nature, nurture

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

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The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Peter Fedichev

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We studied fundamental aspects of aging to develop a mathematical model of gene regulatory network. We show that aging manifests itself as an inherent instability of gene network leading to exponential accumulation of regulatory errors with age. To validate our approach we studied age-dependent omic data such as transcriptomes, metabolomes etc. of different model organisms and humans. We build a computational platform based on our model to identify the targets and biomarkers of aging to design new drugs against aging and age-related diseases. As biomarkers of aging, we choose the rate of aging and the biological age since they completely determine the state of the organism. Since rate of aging rapidly changes in response to an external stress, this kind of biomarker can be useful as a tool for quantitative efficacy assessment of drugs, their combinations, dose optimization, chronic toxicity estimate, personalized therapies selection, clinical endpoints achievement (within clinical research), and death risk assessments. According to our model, we propose a method for targets identification for further interventions against aging and age-related diseases. Being a biotech company, we offer a complete pipeline to develop an anti-aging drug-candidate.

Keywords: aging, longevity, biomarkers, senescence

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Authors: Denys Sebov, Viktoriia Korotaieva, Kateryna Markina

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The clinical advantage of the multipill combination drugs administration (polypill-strategy) over single-component drugs (monopill-strategy) has been established in patients with comorbid arterial hypertension, heart failure, chronic coronary syndrome, diabetes. It was found that polypill-strategy provides better treatment adherence in 33.4% of the patients. It was proven a significant decrease in systolic and diastolic blood pressure, as well as a decrease in dispersion index due to the stability of the blood pressure profile in patients with the polypill-strategy treatment.

Keywords: polypill, artetial hypertension, cardiovascular disease, compliance

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Authors: Rahul Magazine, Shobitha Rao

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The aim of this study was to study the prescribing pattern of drugs in patients with ARDS (Acute Respiratory Distress Syndrome) managed at a tertiary care hospital. This observational study was conducted at Kasturba Hospital, Karnataka, India. Data of patients admitted from January 2010 to December 2012 was collected. A total of 150 patients of ARDS were included. Data included patients’ age, gender, clinical disorders precipitating ARDS, and prescribing pattern of drugs. The mean age of the study population was 42.92±13.91 years. 48% of patients were less than 40 years of age. Infection was the cause of ARDS in 81.3% of subjects. Antibiotics were prescribed in all the subjects and beta-lactams were prescribed in 97.3%. 41.3% were prescribed corticosteroids, 39.3% diuretics and 89.3% intravenous fluids. Infection was the commonest etiology for ARDS, and beta-lactams were the commonest antibiotics prescribed. Corticosteroids and diuretics were prescribed in a significant number of patients. Most of the patients received intravenous fluids.

Keywords: acute respiratory syndrome, beta lactams, corticosteroids, Acute Respiratory Distress Syndrome (ARDS)

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Authors: M. G. Cattaneo

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The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: global health, global justice, patent law reform, access to drugs

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Authors: Chieh-Nan Chen, Ji-Yu Lin, I-Ming Chu

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Polypeptide thermosensitive hydrogel is an excellent candidate as a smart device to deliver drugs and cells due to its remarkable biocompatibility, low gelation concentration, and respond to temperature stimuli, it can be easily injected as a polymer solution into the patient’s body where it undergoes gelation due to an elevation in temperature. Poly (ethylene glycol) monomethyl ether-poly (ethyl-l-glutamate) (mPEG-PELG) contains a hydrophobic side chain –C2H5 which is useful in encapsulating and stabilizing hydrophobic drugs. In this study, we plan to focus on the hydrophobic anti-carcinogenic and anti-inflammatory drug curcumin, which due its insolubility in water, requires a proper carrier for delivery into the body. Our main concept is to use mPEG-PELG to stabilize curcumin, inject the curcumin-loaded hydrogel into the tumor site, and allow the enzymatically-sensitive hydrogel to be degraded by bodily fluids and release the drug. The polymers of interest have been successfully synthesized and characterized by 1H-NMR, FT-IR, SEM, and CMC. Curcumin loading content and drug release were assayed using HPLC. Preliminary results show that these materials have potential as a delivery vehicle for poorly soluble drugs.

Keywords: curcumin, drug release, hydrogel, polypeptide material

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Authors: Yu-Hong Lin

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Background: An adverse drug reaction (ADR) reported is an injury which caused by taking medicines. Sometimes the severity of ADR reported may be minor, but sometimes it could be a life-threatening situation. In order to provide healthcare professionals as a better reference in clinical practice, we do data collection and analysis from our hospital. Methods: This was a retrospective study of ADRs reported performed from 2014 to 2015 in our hospital in Taiwan. We collected assessment items of ADRs reported, which contain gender and age, occurring sources, Anatomical Therapeutic Chemical (ATC) classification of suspected drugs, types of adverse reactions, Naranjo score calculating by Naranjo Adverse Drug Reaction Probability Scale and so on. Results: The investigation included two hundred and seven ADRs reported. Most of ADRs reported were occurring in outpatient department (92%). The average age of ADRs reported was 65.3 years. Less than 65 years of age were in the majority in this study (54%). Majority of all ADRs reported were males (51%). According to ATC classification system, the major classification of suspected drugs was cardiovascular system (19%) and antiinfectives for systemic use (18%) respectively. Among the adverse reactions, Dermatologic Effects (35%) were the major type of ADRs. Also, the major Naranjo scores of all ADRs reported ranged from 1 to 4 points (91%), which represents a possible correlation between ADRs reported and suspected drugs. Conclusions: Definitely, ADRs reported is still an extremely important information for healthcare professionals. For that reason, we put all information of ADRs reported into our hospital's computer system, and it will improve the safety of medication use. By hospital's computer system, it can remind prescribers to think of information about patient's ADRs reported. No drugs are administered without risk. Therefore, all healthcare professionals should have a responsibility to their patients, who themselves are becoming more aware of problems associated with drug therapy.

Keywords: adverse drug reaction, Taiwan, healthcare professionals, safe use of medicines

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Authors: Ana Caroline Ibrahim Lino, Denise Bomtempo Birche de Carvalho

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The background of this research is the international process of control and monitoring of illicit psychoactive substances that has commenced in the early 20th century. This process was intensified with the UN Single Convention on Narcotic Drugs of 1961 and had its culmination in the 1970s with the "War on drugs", a doctrine undertaken by the United States of America. Since then, the phenomenon of drug prohibition has been pushing debates around alternatives of public policies to confront their consequences at a global level and in the specific context of Latin America. Previous research has answered the following key questions: a) With what characteristics and models has the international illicit drug control system consolidated in Latin America with the creation of the Organization of American States (OAS) and the Inter-American Drug Abuse Control Commission (CICAD)? b) What drug policies and programs were determined as guidelines for the member states by the OAS and CICAD? The present paper mainly addresses the analysis of the drug strategies developed by the OAS/CICAD for the Americas from 2004 to 2016. The primary sources have been extracted from the OAS/CICAD documents and reports, listed on the Internet sites of these organizations. Secondary sources refer to bibliographic research on the subject with the following descriptors: illicit drugs, public policies, international organizations, OAS, CICAD, and reducing the demand and supply of illicit drugs. The "content analysis" technique was used to organize the collected material and to choose the axes of analysis. The results show that the policies, strategies, and action plans for Latin America had been focused on anti-drug actions since the creation of the Commission until 2010. The discourses and policies to reduce drug demand and supply were of great importance for solving the problem. However, the real focus was on eliminating the substances by controlling the production, marketing, and distribution of illicit drugs. Little attention was given to the users and their families. The research is of great relevance to the Social Work. The guidelines and parameters of the Social Worker's profession are in line with the need for social, ethical, and political strengthening of any dimension that guarantees the rights of users of psychoactive substances. In addition, it contributed to the understanding of the political, economic, social, and cultural factors that structure the prohibitionism, whose matrix anchors the deprivation of rights and violence.

Keywords: illicit drug policies, international organizations, latin America, prohibitionism, reduce the demand and supply of illicit drugs

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Authors: Emy Nayana Pinto, Denise Bomtempo Birche De Carvalho

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In the present study, the harmful use of illicit drugs is seen as a public health problem and as one of the expressions of the social question, since its consequences fall mainly on the poorer classes of the population. This perspective is a counterpoint to the dominant paradigm on illicit drug policy at the global level, whose centrality lies within the criminal justice arena. The 'drug problem' is internationally combated through fragmented approaches that focus its actions on banning and criminalizing users. In this sense, the research seeks to answer the following key questions: What are the influences of the prohibitionism in the recommendations of the United Nations (UN), the World Health Organization (WHO), and the formulation of drug policies in member countries? What are the actors that have been provoking the prospect of breaking with the prohibitionist paradigm? What is the WHO contribution to the rupture with the prohibitionist paradigm and the displacement of the drug problem in the field of public health? The general objective of this work is to seek evidence from the perspective of rupture with the prohibitionist paradigm in the field of drugs policies at the global and regional level, through analysis of documents of the World Health Organization (WHO), between the years of 2001 to 2016. The research was carried out in bibliographical and documentary sources. The bibliographic sources contributed to the approach with the object and the theoretical basis of the research. The documentary sources served to answer the research questions and evidence the existence of the perspective of change in drug policy. Twenty-two documents of the UN system were consulted, of which fifteen had the contribution of the World Health Organization (WHO). In addition to the documents that directly relate to the subject of the research, documents from various agencies, programs, and offices, such as the Joint United Nations Program on HIV/AIDS (UNAIDS) and the United Nations Office on Drugs and Crime (UNODC), which also has drugs as the central or transversal theme of its performance. The results showed that from the 2000s it was possible to find in the literature review and in the documentary analysis evidence of the critique of the prohibitionist paradigm parallel to the construction of a new perspective for drug policy at the global level and the displacement of criminal justice approaches for the scope of public health, with the adoption of alternative and pragmatic interventions based on human rights, scientific evidence and the reduction of social damages and health by the misuse of illicit drugs.

Keywords: illicit drugs, international organizations, prohibitionism, public health, World Health Organization

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Authors: Alpana Meena

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Background: Tuberculosis is one of the major causes of death in south-east nations. Anti-TB–induced hepatotoxicity (AIH) is associated with a mortality of 6%–12%. The risk is increased when the drugs are combined. Reintroduction of anti-tuberculosis drugs in patients with AIH has never been studied systematically. The present study was planned to see the clinical profile of patients of AIH and the response to reintroduction of therapy. Methods: The trial was conducted in the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, on 32 patients with extra-pulmonary tuberculosis who developed AIH. Patients were randomly allocated into 3 groups. In group 1- Isoniazid (INH) and Rifampicin (RIF) were given at full dosages (weight calculated) from day 1. In group 2- RIF was given at maximum dosage from day 1 and INH at maximum dosage from day 8. In group 3- INH was given at maximum dosage from day 1 and RIF at maximum dosage from day 8. Pyrazinamide was added when above regimens were tolerated. Results: The mean age of presentation was 29.37±13.497 years. The incidence was found to be highest in patients with tubercular meningitis (41%) followed by abdominal, pericardial, disseminated, spinal, and lymph nodes. The mean latent period for development of AIH was 7.84 days ± 6.149 days and the median normalization days for LFT’s was 8.81 ± 4.22 days (3-21). In the study, 21% patients had recurrence of AIH with majority of patients having tolerated the reintroduction of drugs. Pyrazinamide was introduced after establishing isoniazid and rifampicin safety, thus emphasizing the role of gradual reintroduction of ATT to avoid the combined effects of hepatotoxicity. Conclusion: To conclude, the recurrence rate of hepatotoxicity was not statistically significant between the three groups studied (p > 0.05), and thus all 3 hepatotoxic drugs can be reintroduced safely in patients developing AIH.

Keywords: anti-tubercular therapy induced hepatotoxicity, extra-pulmonary tuberculosis, reintroduction regimens, risk factors

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Authors: Shrawan Baghel, Helen Cathcart, Biall J. O'Reilly

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Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form lowers the activation energy barrier for crystallization and thermodynamically drives it towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) has been selected as model compounds. Thermodynamic fragility (m_T) is measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (m_D) is evaluated using methods based on extrapolation of configurational entropy to zero 〖(m〗_(D_CE )), and heating rate dependence of Tg 〖(m〗_(D_Tg)). The mean relaxation time of amorphous drugs was calculated from Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant ‘n’ which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems was also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. In addition, the crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics is found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations.

Keywords: amorphous, fragility, glass forming ability, molecular mobility, mean relaxation time, crystallization kinetics, stability

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Authors: Sachin Saxena, Manju Srivastava

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The present study describes a stable, highly sensitive and selective analytical sensor. Fe-BTC was synthesized at room temperature using the noble Iron-trimesate system. The high surface area of as synthesized Fe-BTC proved MOFs as ideal modifiers for glassy carbon electrode. The characterization techniques such as TGA, XRD, FT-IR, BET (BET surface area= 1125 m2/gm) analysis explained the electrocatalytic behaviour of Fe-BTC towards these two drugs. The material formed is cost effective and exhibit higher catalytic behaviour towards analyte systems. The synergism between synthesized Fe-BTC and electroanalytical techniques helped in developing a highly sensitive analytical method for studying the redox fate of ARP and RZ, respectively. Cyclic voltammetry of ferricyanide system proved Fe-BTC/GCE with an increase in 132% enhancement in peak current value as compared to that of GCE. The response characteristics of cyclic voltammetry (CV) and square wave voltammetry (SWV) revealed that the ARP and RZ could be effectively accumulated at Fe-BTC/GCE. On the basis of the electrochemical measurements, electrode dynamics parameters have been evaluated. Present study opens up new field of applications of MOFs modified GCE for drug sensing.

Keywords: MOFs, anti-psychotic, electrochemical sensor, anti-migraine drugs

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