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New Drug Development

Daiane Anzilaggo, André O'Reilly Beringhs, Bianca Ramos Pezzini, Diva Sonaglio, Hellen Karine Stulzer
The drug in a solid dosage form must undergo dissolution before it is available for absorption from the gastrointestinal tract. Liquisolid system (LS) is a technology used for increasing aqueous solubility of the drugs, which has an important role in the dissolution and absorption phenomena. However, many factors can influence the performance and success of LS. Therefore this study aimed to evaluate through a factorial design, the factors such as drug state (solution or dispersion), nonvolatile solvent and coating material that influence the increase simvastatin (BSC II drug) apparent aqueous solubility and LS flow properties...
November 22, 2018: Colloids and Surfaces. B, Biointerfaces
Mahfuz Al Mamun, Kaiissar Mannoor, Jun Cao, Firdausi Qadri, Xiaoyuan Song
Cancer stem cells (CSCs), a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors, posit a significant challenge to develop effective and long-lasting anti-cancer therapies. The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs, thereby leading to CSC-mediated clinical relapse. Accumulating evidence suggests that transcription factor SOX2, a master regulator of embryonic and induced pluripotent stem cells, drives cancer stemness, fuels tumor initiation, and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition (EMT), ATP-binding cassette (ABC) drug transporters, anti-apoptotic and/or pro-survival signaling, lineage plasticity, and evasion of immune surveillance...
December 5, 2018: Journal of Molecular Cell Biology
Angela Mazzeo, Enrico Jardim Clemente Santos
The biology of stem cells is one of the most dynamic and promising fields of the biological sciences, since it is the basis for the development of organisms. Its biological complexity demands efforts from several lines of research aimed mainly at its therapeutic use. Nanotechnology has been emerging as a new field of study, which shows great potential in the treatment of various diseases. This new area of health has been called "Nanomedicine" or "Bionanotechnology", which can be applied in Medicine by transport and drug delivery systems, robotic tools to be used in diagnostic and surgical processes, nanobiomaterials, gene therapies, nanobiomedical devices, among others...
November 29, 2018: Einstein
Maria Yousuf, Nimra Naveed Shaikh, Zaheer Ul-Haq, M Iqbal Choudhary
Identification of hotspot drug-receptor interactions through in-silico prediction methods (Pharmacophore mapping, virtual screening, 3DQSAR, etc), is considered as a key approach in drug designing and development process. In the current design study, advanced in-silico based computational techniques were used for the identification of lead-like molecules against the targeted receptor β-glucuronidase. The binding pattern of a potent inhibitor in the ligand-receptor X-ray co-crystallize complex was used to identify and extract the structure-base Pharmacophore features...
2018: PloS One
Michael R Hamblin
The prognosis for severe burns has improved significantly over the past 50 years. Meanwhile, burns have become an affliction mainly affecting the less well-developed regions of the world. Early excision and skin grafting has led to major improvements in therapeutic outcomes. Areas covered: The purpose of this article is to survey the use of pharmacotherapy to treat different pathophysiological complications of burn injury. The author, herein, discusses the use of drug treatments for a number of systemic metabolic disturbances including hyperglycemia, elevated catabolism, and gluconeogenesis...
December 5, 2018: Expert Opinion on Pharmacotherapy
Kouta Sugikawa, Kotaro Matsuo, Atsushi Ikeda
Suppression of nanoparticle aggregation on a plasma membrane surface may lead to better understanding of the causes of various diseases and development of new drug delivery systems. In this study, we inhibited the aggregation of gold nanoparticles on a lipid membrane in a fluidic liquid-crystalline phase by using nanosized liposomes to increase steric hindrance. Adsorption of liposomes on gold nanoparticles was confirmed by transmission electron microscopy and ultraviolet-visible absorption spectroscopy. The ability of the liposomes to suppress gold nanoparticle aggregation strongly depended on the concentration of liposomes providing steric hindrance...
December 5, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Ali Çoner, Davran Çiçek, Sinan Akıncı, Serhat Balcıoğlu, Cihan Altın, Haldun Müderrisoğlu
OBJECTIVE: Diffuse coronary artery disease (CAD) is a challenging issue in clinical cardiology practice. There are limited data about percutaneous revascularization in these patients. METHODS: This study was an observational clinical evaluation. The records of patients with diffuse CAD revascularized with new-generation drug-eluting stents (DES) were researched retrospectively. Patients treated with multiple, overlapping new-generation DES (at least 60mm in length per vessel) were included...
December 2018: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Judy W M Cheng, Vincent J Colucci, James S Kalus, Sarah A Spinler
OBJECTIVE: While improving glycemic control with antihyperglycemics has been demonstrated to reduce microvascular complications, the benefits of reduction in cardiovascular diseases (CVDs) have not been demonstrated with older agents. This article reviews current evidence of the CV outcomes of newer antihyperglycemics approved since 2008. DATA SOURCES: Peer-reviewed articles were identified from MEDLINE (1966 to October 31, 2018) using search terms exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, mortality, myocardial infarction (MI), heart failure (HF), and stroke...
December 5, 2018: Annals of Pharmacotherapy
Toshifumi Wakai, Pankaj Prasoon, Yuki Hirose, Yoshifumi Shimada, Hiroshi Ichikawa, Masayuki Nagahashi
Numerous technical and functional advances in next-generation sequencing (NGS) have led to the adoption of this technique in conventional clinical practice. Recently, large-scale genomic research and NGS technological innovation have revealed many more details of somatic and germline mutations in solid tumors. This development is allowing for the classification of tumor type sub-categories based on genetic alterations in solid tumors, and based on this information, new drugs and targeted therapies are being administered to patients...
December 4, 2018: International Journal of Clinical Oncology
Artem Lysenko, Alok Sharma, Keith A Boroevich, Tatsuhiko Tsunoda
Recent trends in drug development have been marked by diminishing returns caused by the escalating costs and falling rates of new drug approval. Unacceptable drug toxicity is a substantial cause of drug failure during clinical trials and the leading cause of drug withdraws after release to the market. Computational methods capable of predicting these failures can reduce the waste of resources and time devoted to the investigation of compounds that ultimately fail. We propose an original machine learning method that leverages identity of drug targets and off-targets, functional impact score computed from Gene Ontology annotations, and biological network data to predict drug toxicity...
December 2018: Life science alliance
Mingsong Shi, Dingguo Xu, Jun Zeng
Quantum mechanical approaches for the massive computation on large biological system such as virtual screening in drug design and development have presented a challenge to computational chemists for many years. In this study, we demonstrated that by taking advantage of rapid growth of GPU-based hardware and software (i.e., teraChem), it is feasible to perform virtual screening of a refined chemical library at quantum mechanical level in order to identify the lead compounds with improved accuracy, especially for the drug targets such as metalloproteins in which significant charge transfer and polarization occur amongst the metal ions and their coordinated amino acids...
2018: Frontiers in Chemistry
Marilyn J Telen, Punam Malik, Gregory M Vercellotti
For over 100 years, clinicians and scientists have been unravelling the consequences of the A to T substitution in the β-globin gene that produces haemoglobin S, which leads to the systemic manifestations of sickle cell disease (SCD), including vaso-occlusion, anaemia, haemolysis, organ injury and pain. However, despite growing understanding of the mechanisms of haemoglobin S polymerization and its effects on red blood cells, only two therapies for SCD - hydroxyurea and L-glutamine - are approved by the US Food and Drug Administration...
December 4, 2018: Nature Reviews. Drug Discovery
Aanchal Kashyap, Pankaj Kumar Singh, Om Silakari
Tuberculosis (TB) is contagious in nature and immunocompromised patients have a higher probability of developing TB. The occurrence of drug resistance, has led to serious health concerns in the management of TB. In order to combat resistant tuberculosis there is an urgent need of identifying new drug targets and new drug combinations for the effective management and reduction in the duration of TB treatment. Targeting DNA gyrase that is involved in bacterial replication cycle, provides one rationale approach...
December 2018: Tuberculosis
Erik Tenland, Nitya Krishnan, Anna Rönnholm, Sadaf Kalsum, Manoj Puthia, Matthias Mörgelin, Mina Davoudi, Magdalena Otrocka, Nader Alaridah, Izabela Glegola-Madejska, Erik Sturegård, Artur Schmidtchen, Maria Lerm, Brian D Robertson, Gabriela Godaly
Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate by screening antimicrobial peptides for their capacity to inhibit mycobacterial growth. This non-toxic peptide, NZX, is capable of inhibiting both clinical strains of M...
December 2018: Tuberculosis
Musa Marimani, Aijaz Ahmad, Adriano Duse
Tuberculosis (TB) infection caused by Mycobacterium tuberculosis (Mtb) is still a persistent global health problem, particularly in developing countries. The World Health Organization (WHO) reported a mortality rate of about 1.8 million worldwide due to TB complications in 2015. The Bacillus Calmette-Guérin (BCG) vaccine was introduced in 1921 and is still widely used to prevent TB development. This vaccine offers up to 80% protection against various forms of TB; however its efficacy against lung infection varies among different geographical settings...
December 2018: Tuberculosis
Zacharie Segaoula, Aline Primot, Frederic Lepretre, Benoit Hedan, Emmanuel Bouchaert, Kevin Minier, Laurent Marescaux, François Serres, Sylvie Galiègue-Zouitina, Catherine André, Bruno Quesnel, Xavier Thuru, Dominique Tierny
BACKGROUND: Metastatic melanoma is one of the most aggressive forms of cancer in humans. Among its types, mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. Because they are rare in Caucasian individuals, unlike cutaneous melanomas, there has been fewer epidemiological, clinical and genetic evaluation of mucosal melanomas. Moreover, the lack of predictive models fully reproducing the pathogenesis and molecular alterations of mucosal melanoma makes its treatment challenging...
December 4, 2018: BMC Cancer
Zhiyang Li, Chuqing Liu, Victor Sarpong, Zhiyong Gu
Antibiotics such as penicillin and tetracycline drugs are widely used in food animals to treat, control, and prevent diseases, and penicillin is approved for use to improve growth rates in pigs and poultry. However, due to the overuse of antibiotics in food and medical industry, the antimicrobial resistance is starting to show up in some developing countries. The antibiotic abuse may cause allergic reactions, resistance in microorganisms and general lowering of immunity in consumers of meat and dairy products...
October 17, 2018: Biosensors & Bioelectronics
Prasanthi Polamreddy, Nandu Gattu
As the name suggests, drug repurposing is a strategy to identify new therapeutic uses for marketed drugs, discontinued and/or shelved drugs, and drug candidates currently in clinical development. Although not a recent concept, drug repurposing has gained momentum over the past few years and several drugs have been successfully repurposed. Here, we summarize the drug repurposing landscape from 2012 to 2017, with a major focus on repurposed drugs, collaborative opportunities, and funding opportunities specific to drug repurposing projects...
December 1, 2018: Drug Discovery Today
Timothy P Maus, Joel P Felmlee, Mark D Unger, Andreas S Beutler
BACKGROUND: Development of new analgesic drugs or gene therapy vectors for spinal delivery will be facilitated by "hyperlocal" targeting of small therapeutic injectate volumes if spine imaging technology can be used that is ready for future clinical translation. NEW METHOD: This study provides methods for MRI-guided drug delivery to the periganglionic epidural space and the dorsal root ganglion (DRG) in the Yucatan swine. RESULTS: Phantom studies showed artifact-corrected needle localization with frequency encoding parallel to the needle shaft, while maximizing bandwidth (125 KHz) minimized needle artifact...
December 1, 2018: Journal of Neuroscience Methods
Juan Martin-Liberal, Ezequiel Pérez, Xavier García Del Muro
Soft-tissue sarcomas (STS) are a heterogeneous group of diseases that are characterized by a historic lack of active treatment options. However, several new drugs and indications have become available in recent years. Areas covered: This article reviews the most relevant phase II studies that utilize chemotherapy agents (aldoxorubicin, amrubicin, trabectedin alone or in combination with doxorubicin, and gemcitabine plus docetaxel), targeted therapies (Imatinib, dasatinib, regorafenib, tivozanib, palbociclib and selinexor), a combination of chemotherapy plus targeted therapies (fucusing on doxorubicin plus olaratumab) and immunotherapies (pembrolizumab, combination of nivolumab plus ipilimumab and adaptive cell therapy) in STS (other than gastrointestinal stromal tumors) (GIST) published from 2015...
December 4, 2018: Expert Opinion on Investigational Drugs
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