Editor’s Choice – “Solid State Concerns During Drug Discovery and Development: Thermodynamic and Kinetic Aspects of Crystal Polymorphism and the Special Cases of Concomitant Polymorphs, Co-Crystals and Glasses”

Journal: Current Drug Discovery Technologies

Author(s): Daniel P. Otto, Melgardt M. De Villiers

Graphical Abstract:


During drug discovery and development the thermodynamics and kinetics of crystal form transitions must be studied and the fundamental properties of polymorphs must be identified. However, despite the accumulation of knowledge and experimental evidence that support the understanding of crystallization, its predictability still presents significant challenges. With the continuous development of new drug delivery technologies, even more complex situations arise such as difficult cases of polymorph selection, co-crystallization of different molecules, and manipulation of the crystallization environment for example amorphous solids. This review covers some fundamental thermodynamics and kinetics of simple system, before the discussions consider at these special cases and how the manipulation of thermodynamic and kinetic processes has increased our knowledge, understanding and application of crystallization science during the drug development process.

Read more here: http://www.eurekaselect.com/147852

Editor’s Choice – “Synovial Inflammation Drives Structural Damage in Hand Osteoarthritis: a Narrative Literature Review”

Journal: Current Rheumatology Reviews

Author(s): Luana Mancarella, Olga Addimanda, Carlotta Cavallari, Riccardo Meliconi

Graphical Abstract:


Background: Ultrasound is one of the most promising candidates for the detection of inflammation and structural damage in hand osteoarthritis.

Objective: To evaluate new advances of US as a diagnostic and prognostic tool in hand osteoarthritis assessment.

Methods: We conducted a Medline on PubMed search for articles about “ultrasonography” and “hand OA” published between January 2012 and 15th April 2016, limiting our search to articles on human adults in English, excluding those involving systemic inflammatory diseases, visualization of joints other than hands, ultrasound guided injections and surgical procedures. Reviews, case reports, letters, position statements and ex vivo studies were excluded. Concordance between ultrasound and conventional radiography and magnetic resonance imaging was evaluated.

Results: Total 46 records were identified, and 16 articles were selected: four showed only ultrasound structural damage (osteophytes, cartilage pathology), six only ultrasound inflammatory variables (synovial thickness, effusion and power Doppler signal), six should considered both ultrasound structural and inflammatory features as well as erosions and two were epidemiological studies. Ultrasound synovitis and power Doppler signal were more frequent in erosive hand osteoarthritis. Followup studies found that ultrasound inflammatory features at baseline are independently associated with radiographic progression; power Doppler signal was the strongest predictor of structural damage. Ultrasound is a reliable tool for cartilage and osteophyte assessment (when performed with static images) and shows a good concordance with magnetic resonance imaging for osteophytes, erosions and synovitis.

Conclusions: Ultrasound detected inflammation may predict radiographic progression and may be used in prospective clinical trials of hand osteoarthritis and in everyday clinical practice.

Read more here: http://www.eurekaselect.com/145495 

Editor’s Choice – “pH-Sensitive Polymeric Nanoparticles Fabricated by Dispersion Polymerization for the Delivery of Bioactive Agents”

Journal: Pharmaceutical Nanotechnology

Author(s): Reema Puri, Solomon A. Berhe, Emmanuel O. Akala

Graphical Abstract:



Background: Development of pH-responsive nanoparticles capable of rapid degradation in the acidic environments in the endosomes and lysosomes of tumor tissues but relatively more stable in the physiological pH (pH 7.4) is desirable.

Objective: To show that the number of methoxy groups on the benzene ring of benzaldehyde bisacrylate acetal crosslinkers should affect the rate of hydrolysis of the crosslinkers and in vitro availability of the drug loaded into the nanoparticles.

Method: Three pH-sensitive acetal crosslinkers were synthesized and characterized by 1H NMR, 13C NMR, FT-IR and high resolution mass spectroscopy (HR-MS). The nanoparticles were fabricated by free-radical dispersion polymerization method. Hydrolysis studies were carried out on the crosslinkers and nanoparticles; drug release studies were done on docetaxel-loaded nanoparticles at pH 5.0 and pH 7.4. The statisitical experimental design was randomized complete block design followed by analyses of variance with F-test of significance. Pairwise comparison test was used to locate specific differences among parameters of the crosslinkers and the nanopaticles.

Results: Scanning electron micrographs showed the formation of spherical particles. Particle size analysis showed that the nanoparticles are within nanosize range with negative zeta potential. Data showed that the rate of hydrolysis and drug release were faster at pH 5.0 compared to pH 7.4. Hydrolysis and drug release studies were dependent on the structure of the acetals: Di(2-methacryloyloxyethoxy)- [2,4,6-trimethoxyphenyl] methane crosslinker showed the fastest rate of hydrolysis, followed by di(2- methacryloyloxyethoxy)-[2,4-dimethoxyphe-nyl] methane and di(2-methacryloyloxyethoxy)-[4-methoxyphenyl] methane.

Conclusion: The pH-responsive nanoparticles are suitable for the delivery of bioactive agents, especially anticancer drugs.

Read more here: http://www.eurekaselect.com/149109

Editor’s Choice – “Ganoderma lucidum (Ling-zhi): The Impact of Chemistry on Biological Activity in Cancer”

Journal: Current Bioactive Compounds

Author(s): Temitope O. Lawal, Sheila M. Wicks, Gail B. Mahady

Graphical Abstract:



Background: Ganoderma (Ganodermataceae), a genus of medicinal mushrooms, has been employed as an herbal medicine in Traditional Chinese medicine (TCM) for over 2000 years. The fruiting bodies have been used historically in TCM, while the mycelia, and spores are now also used as a tonic, to stimulate the immune system and treat many diseases, including cancers.

Objective: To review the anti-cancer research on G. lucidum (GL) from 2005 up to May 2016 and correlate these data with analysis of the active chemical constituents.

Methods: Literature searches were performed from 2005 to May 2016 in various databases such as Pub- Med, SciFinder, Napralert, and Google Scholar for peer-reviewed research literature pertaining to Ganoderma lucidum and cancer.

Results: Of the >200 known Ganoderma species, only two species, G. lucidum (W. Curtis: Fr.) P. Karst and G. sinense Zhao, Xu et Zhang, are officially recognized as “Ling-zhi” in the Chinese Pharmacopoeia. Both species are thought to have similar biological effects. “Ling-zhi” is purported to have anticancer effects, and is also used in the promotion of health and longevity. Numerous polysaccharides and triterpenes have been identified in G. lucidum and have anticancer effects in both cell culture and animal models.

Conclusion: The current published literature suggests that G. lucidum extracts have excellent potential for use in cancer therapy, as both the triterpenes and polysaccharides appear to have anti-cancer effects both in vitro and in vivo. However, many problems still exist including significant quality issues including taxonomy and identification of species, parts used, and the production of extracts with active constituents.

Read more here: http://www.eurekaselect.com/143264 


Editor’s Choice – “Right Heart Catheterization Through Persistent Left Superior Vena Cava, an Extremely Rare Procedure and Review of Current Literature”

Journal: Current Cardiology Reviews

Author(s): Nattapong Sricharoen, Mohammad Chamsi-Pasha, Ahmed Sami Abuzaid, Abdel Rahman Al Emam


Graphical Abstract:



Persistent left superior vena cava (PLSVC) is encountered occasionally during angiographic procedures. It usually coexists with right superior vena cava and drains to the right atrium through the coronary sinus, but multiple variations are described. Although PLSVC is extensively reported in the literature, there are very few articles addressing right heart catheterization in patients with isolated PLSVC. We present a patient with absent right superior vena cava and PLSVC draining to a dilated coronary sinus diagnosed during right heart catheterization in the setting of pulmonary hypertension. We were able to safely complete the procedure through the right internal jugular vein. Transthoracic echocardiography and chest CT scan were consistent with this finding. Although clinically silent most of the time, undiagnosed PLSVC can lead to catastrophic consequences when the patient undergoes invasive procedures. If PLSVC is suspected, the anatomy of the thoracic venous system must be identified before invasive cardiac procedures.

Read more here: http://www.eurekaselect.com/146803

Editor’s Choice – “The Status of Methicillin Resistance Among Egyptian Staphylococcus aureus Isolates: An Overview”

Journal: Infectious Disorders – Drug Targets

Author(s): Alaa Abouelfetouh



Methicillin resistant Staphylococcus aureus (MRSA) is responsible for a large number of antibiotic resistant infections worldwide. Understanding the epidemiology and identifying the molecular characteristics of MRSA is elemental in designing infection control plans to minimize the risks associated with these infections. The prevalence of MRSA varies between the different geographic regions. In Egypt, such knowledge is sparse, with a limited number of isolated studies reporting the infection rate of MRSA in select parts of the country. This work summarizes the few published reports that described MRSA prevalence and types in Egypt.

Read more here: http://www.eurekaselect.com/144438

Editor’s Choice – “Hitting a Moving Target: Glioma Stem Cells Demand New Approaches in Glioblastoma Therapy”

Journal: Current Cancer Drug Targets

Author(s): Drew A. Spencer, Brenda M. Auffinger, Jason P. Murphy, Megan E. Muroski, Jian Qiao, Yureve Gorind, Maciej S. Lesniak



Background: Glioblastoma multiforme (GBM) continues to devastate patients and outfox investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably recurring in a yet more aggressive and resistant form with distinct genetic differences from the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation of cells with a stem-like phenotype. These cancer stem cells, similar to those now described in a variety of malignancies, are capable of tumorigenesis from a population of susceptible cells.

Conclusions: Glioma stem cells have thus become a prevalent focus in GBM research for their presumed role in development, maintenance and recurrence of tumors. Glioma stem cells infiltrate the white matter surrounding tumors and often evade resection. They are uniquely suited both biochemically and environmentally to resist the best therapy currently available, intrinsically and efficiently resistant to standard chemo- and radiotherapy. These stem cells create an extremely heterogenous tumor that to date has had an answer for every therapeutic question, with continued dismal patient survival. Targeting this population of glioma stem cells may hold the long-awaited key to durable therapeutic efficacy in GBM.

Read more here: http://www.eurekaselect.com/148386


Editor’s Choice – “Use of Recursive Partitioning Analysis in Clinical Trials and Meta-Analysis of Randomized Clinical Trials, 1990-2016”

Journal: Reviews on Recent Clinical Trials

Author(s): Martha Maria Fors, Carmen Elena Viada, Paloma Gonzalez

Graphical Abstract:



Background: Recursive Partitioning Analysis (RPA) is a very flexible non parametric algorithm that allows classification of individuals according to certain criteria, particularly in clinical trials, the method is used to predict response to treatment or classify individuals according to prognostic factors.

Objectives: In this paper we examine how often RPA is used in clinical trials and in meta-analysis.

Methods: We reviewed abstracts published between 1990 and 2016, and extracted data regarding clinical trial phase, year of publication, type of treatment, medical indication and main evaluated endpoints.

Results: One hundred and eighty three studies were identified; of these 43 were meta-analyses and 23 were clinical trials. Most of the studies were published between 2011 and 2016, for both clinical trials and meta-analyses of randomized clinical trials. The prediction of overall survival and progression free survival were the outcomes most evaluated, at 43.5% and 51.2% respectively. Regarding the use of RPA in clinical trials, the brain was the most common site studied, while for meta-analytic studies, other cancer sites were also studied. The combination of chemotherapy and radiation was seen frequently in clinical trials.

Conclusion: Recursive partitioning analysis is a very easy technique to use, and it could be a very powerful tool to predict response in different subgroups of patients, although it is not widely used in clinical trials.

Read more here: http://www.eurekaselect.com/145588 


Editor’s Choice – “Novel Fluorescent Benzimidazoles: Synthesis, Characterization, Crystal Structure and Evaluation of Their Anticancer Properties”

Journal: Letters in Organic Chemistry

Author(s):  Yeong Keng Yoon, Tze Shyang Chia, Ching Kheng Quah, Wan Leng Lim, Chuan Wei Oo, Amir Nasrolahi Shirazi, Keykavous Parang,Tan Soo Choon



Background: The benzimidazole core structure is an interesting platform for drug discovery since it possess a wide spectrum of pharmacological activities such as antiviral, anti-inflammatory and anticancer. Previously the antiproliferative effect of novel substituted benzimidazole derivative was demonstrated based on the ethyl 1-(2-hydroxyethyl)-2-phenyl-1H-benzo[d]imidazole-5-carboxylate scaffold through the inhibition of sirtuin activity. This work aimed to further explore the previous work for identifying novel fluorescent benzimidazoles which possess anti proliferative activities based on the reported scaffold.

Methods: Compounds were synthesized based on a multistep but facile protocol. Structure of the compounds was elucidated using NMR, FT-IR, LC-MS, elemental analysis and unambiguously confirmed through crystal X-ray diffraction. Molar extinction coefficient of the autofluorescence compounds were determined using UV spectroscopy while cancer cell growth inhibitory activity was carried out using MTS assay.

Results: Four novel benzimidazole derivatives were successfully synthesized in this study. All four compounds were found to emit blue fluorescence when light-irradiated with molar extinction coefficient ranging from 21000 to 29000 (mol L-1)-1cm-1. Two of the synthesized compounds showed good anti proliferative activity against four cancer cell lines tested in this study.

Conclusion: Four novel benzimidazole derivatives presented in this study were synthesized using multistep protocol starting from 4-fluoro-3-nitrobenzoic acid. Their structures have been elucidated using multiple techniques such as NMR, FT-IR, LC-MS, elemental analysis and X-ray crystallography where possible. They were found to have high autofluorescence and two of them were able to inhibit the growth of cancer cells tested in this study.

Read more here: http://www.eurekaselect.com/147990

Editor’s Choice – “Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid”

Journal: Current Drug Delivery

Author(s): Tiziana M.G. Pecora, Teresa Musumeci, Lucrezia Musumeci, Massimo Fresta, Rosario Pignatello.



Background: Microencapsulation of natural antioxidants in polymeric systems represents a possible strategy for improving the oral bioavailability of compounds that are otherwise poorly soluble.

Objective: α-lipoic acid (ALA) was microencapsulated with polymethacrylate polymers (blends at various ratios of Eudragit® RS100 and RL100 resins).

Method: Microspheres were produced by solvent displacement of an ethanol cosolution of ALA and polymers; the microsuspensions were then freeze-dried, using trehalose as a cryoprotector. Microspheres were characterized in the solid state for micromeritic properties and drug loading, as well as by infrared spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The antioxidant activity of free and encapsulated ALA was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay.

Results: In vitro release studies, performed in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8), showed that, depending on polymer composition and drug-to-polymer ratio, ALA release can be slowed down, compared to the dissolution pattern of the free drug. Solid-state characterization confirmed the chemical stability of ALA in the microspheres, suggesting that ALA did not develop strong interactions with the polymer and was present in an amorphous or a disordered-crystalline state within the polymer network. As indicated by the DPPH assay, the microencapsulation of ALA in Eudragit® Retard matrices did not alter its antioxidant activity.

Conclusion: ALA was effectively encapsulated in Eudragit® Retard matrices, showing a chemical stability up to 6 months at room conditions and at 40°C. Moreover, since the drug maintained its antioxidant activity in vitro, the potential application of these microparticulate systems for oral administration would deserve further studies.

Read more here: http://www.eurekaselect.com/135836/article