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Current Opinion in Pharmacology

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https://www.readbyqxmd.com/read/28892801/minimally-invasive-probes-for-programmed-microfluidic-delivery-of-molecules-in-vivo
#1
REVIEW
Jordan G McCall, Jae-Woong Jeong
Site-specific drug delivery carries many advantages of systemic administration, but is rarely used in the clinic. One limiting factor is the relative invasiveness of the technology to locally deliver compounds. Recent advances in materials science and electrical engineering allow for the development of ultraminiaturized microfluidic channels based on soft materials to create flexible probes capable of deep tissue targeting. A diverse set of mechanics, including micro-pumps and functional materials, used to deliver the drugs can be paired with wireless electronics for self-contained and programmable operation...
September 8, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28892800/polymeric-nanoparticle-constructs-as-devices-for-antibacterial-therapy
#2
REVIEW
Ortensia Ilaria Parisi, Luca Scrivano, Maria Stefania Sinicropi, Francesco Puoci
Diseases related to bacterial infections represent a relevant challenge for public health. Despite the success obtained with the conventional antibiotic therapies, indeed, new drawbacks have been identified. In addition to poor drugs solubility and stability, adverse side effects, and many other factors which together lead to a low patient compliance, the antibiotic resistance and the lack in the development of new antimicrobial agents are the main problems. On the basis of these considerations, the research interest is focused on the exploration of new strategies able to circumvent these drawbacks improving the efficacy of current antibiotics...
September 7, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28888214/catching-new-targets-in-metabolic-disease-with-a-zebrafish
#3
REVIEW
Margrit Kamel, Nikolay Ninov
Traditionally, the development of novel therapeutics for metabolic diseases has relied mainly on high-throughput screening using biochemical or cell-based assays. While this approach represents a driving force in drug discovery, there is also a need to perform large-scale screens without disrupting inter-organ communication and tissue architecture, essential components for understanding the complexity of metabolic regulation and the identification of small molecules with appropriate biological activities in vivo...
September 6, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28881252/bone-derived-exosomes
#4
REVIEW
Jin Liu, Defang Li, Xiaohao Wu, Lei Dang, Aiping Lu, Ge Zhang
Exosomes are endosomal-derived vesicles secreted by a wide range of cell types for transporting functional proteins, microRNAs (miRNAs) and messenger RNAs (mRNA) from their parental cells to affect the recipient cells. Emerging evidence indicates that exosomes also play an important role in the intercellular communication among the bone cells, that is, osteoblasts, osteoclasts and bone marrow stromal cells, within bone microenvironment. Here, we reviewed the local and systemic effects of bone-derived exosomes, and discussed the potential of exosomes as targeted delivery systems for molecular therapy in skeletal disorders...
September 4, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28874314/drug-discovery-for-the-treatment-of-substance-use-disorders-novel-targets-repurposing-and-the-need-for-new-paradigms
#5
REVIEW
Cristiano Chiamulera, Laura Padovani, Mauro Corsi
Drug addiction treatment medications available nowadays are limited in both efficacy and number. The increased understanding of drug addiction circuitries leads the scientific community to look for better molecules and targets for detoxification and relapse prevention. This review focus on known targets (e.g., metabotropic glutamate receptor 5 and GABAB receptor) and on novel potential treatment acting on oxytocin system, which interacts with diverse neurotransmitters, has proved successful in both preclinical and clinical studies on ethanol, cocaine and methamphetamine...
September 2, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28865291/advances-in-polymeric-islet-cell-encapsulation-technologies-to-limit-the-foreign-body-response-and-provide-immunoisolation
#6
REVIEW
Alan J Ryan, Hugh S O'Neill, Garry P Duffy, Fergal J O'Brien
Islet transplantation for the treatment of type 1 diabetes (T1D) is hampered by the shortage of donor tissue and the need for life-long immunosuppression. The engineering of materials to limit host immune rejection opens the possibilities of utilising allogeneic and even xenogeneic cells without the need for systemic immunosuppression. Here we discuss the most recent developments in immunoisolation of transplanted cells using advanced polymeric biomaterials, utilising macroscale to nanoscale approaches, to limit aberrant immune responses...
August 30, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28864032/in-memory-of-norman-bowery-1944-2016
#7
REVIEW
David G Trist, Terry P Kenakin, Thomas P Blackburn
This article is in memory of Professor Norman Bowery (1944-2016). Norman was a pharmacologist who spent most of his career researching the pharmacology of γ-aminobutyric acid (GABA). He discovered a novel metabotropic receptor subtype, GABAB, that is pharmacologically, and structurally different from the original ionotropic receptor now designated as GABAA. In his research he also studied the neurotransmitters glutamate and substance P, two molecules whose release in parts of the spinal cord is inhibited by baclofen a GABAB receptor agonist...
August 29, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28850875/intestinal-patch-systems-for-oral-drug-delivery
#8
REVIEW
Amrita Banerjee, Samir Mitragotri
Intestinal patches provide a unique platform for oral delivery of drugs which possess poor oral bioavailability, necessitating their administration by injections. Intestinal patch based devices prevent drug degradation in the gastrointestinal tract, facilitate their intestinal absorption through forming a localized drug depot at the delivery site and provide unidirectional, controlled drug release while preventing luminal drug loss. Consequently, intestinal patch-based devices are being developed for oral delivery of several drugs such as insulin, exenatide, calcitonin, interferon-α, erythropoietin and human granulocyte colony-stimulating factor for the treatment of diabetes, osteoporosis, hepatitis or for chemotherapy...
August 26, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28846876/inhalation-delivery-of-complex-drugs-the-next-steps
#9
REVIEW
Wilbur de Kruijf, Carsten Ehrhardt
Oral inhalation offers the opportunity of targeting drugs locally to different regions of the respiratory tract or alternatively, using the high surface area of the alveoli for systemic delivery. Pulmozyme and the inhaled insulins (i.e. Exubera and Afrezza) are examples of the scope of pulmonary drug delivery of biopharmaceuticals-albeit with strikingly different commercial success. Particularly, the failure of Exubera and the subsequent overreactions (e.g. the unsubstantiated lung cancer fear), lastingly stunned the field of systemically inhaled protein and peptide drugs...
August 25, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28843953/adipose-tissue-inflammation-in-obesity-a-metabolic-or-immune-response
#10
REVIEW
Emilie Stolarczyk
Adipose tissue is not only a reservoir for energy, but also an immune organ. In the context of obesity, the development of insulin resistance is now recognised to be initiated by inflammation of the adipose tissue. However, the primary events triggering this inflammation are still unclear, as a complex combination of endocrine and immune factors act to regulate this adipose tissue microenvironment. Below we discuss the different factors involved and how they affect the biology of the adipose tissue in obesity...
August 24, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28843865/drug-device-combination-approaches-for-delivery-to-the-eye
#11
REVIEW
Ilva D Rupenthal
While the eye is readily accessible from the outside of the body, it is a rather isolated organ with a number of barriers and elimination mechanisms in place to protect it from the environment, rendering efficient treatment difficult. To enhance drug delivery to the eye, a number of drug-device combinations have been investigated over recent decades, increasing drug retention and permeation while also allowing for sustained drug release over prolonged periods. This article will summarize recent combination systems investigated for the treatment of anterior and posterior segment conditions...
August 24, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28826602/excitatory-and-inhibitory-amino-acid-neurotransmitters-in-stroke-from-neurotoxicity-to-ischemic-tolerance
#12
REVIEW
Diana Amantea, Giacinto Bagetta
The search for neuroprotection in acute ischemic stroke has been dramatically disappointing, with virtually all clinical trials failed for excessive toxicity or lack of efficacy of the tested drug; whereby, current treatments are exclusively based on reperfusion. Given the crucial role of amino acid neurotransmission in ischemic pathobiology, numerous failed strategies were aimed at blocking ionotropic glutamate receptor-mediated excitotoxicity or potentiating GABA-mediated inhibition. Recent work has revived the interest of pharmacologists toward glutamate and GABA receptors, due to a better understanding of subtype-specific toxicity and their involvement in ischemic tolerance...
August 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28822847/intestinal-adaptations-following-bariatric-surgery-towards-the-identification-of-new-pharmacological-targets-for-obesity-related-metabolic-diseases
#13
REVIEW
Lara Ribeiro-Parenti, Jean-Baptiste Cavin, Maude Le Gall
Although the gastrointestinal tract is the primary target of bariatric surgery, its contributions to the metabolic changes observed after surgery are still underestimated. Changes in the number of incretin-producing cells could result in the modified hormonal response seen after surgery. Additionally, the rate of absorption and consumption of glucose could contribute to the ameliorated glycaemia. Moreover, decreased intestinal permeability could prevent endotoxemia. Recently, numerous studies have focused on intestinal adaptation following bariatric surgeries...
August 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28822846/islet-g-protein-coupled-receptors-therapeutic-potential-for-diabetes
#14
REVIEW
Shanta J Persaud
The incidence of type 2 diabetes (T2D) is increasing at an alarming rate, which is imposing substantial healthcare and economic burdens worldwide. T2D can be treated by a range of drugs, but there is a need to identify additional therapeutic options. Human islets express nearly three hundred G-protein-coupled receptors (GPCRs), which could be targeted for the treatment of T2D. However, to date, the GLP-1 receptor is the only islet GPCR for which agonists are in current clinical use. This review explores pharmaceutical development of drugs that activate individual or multiple β-cell GPCRs and explains how our knowledge of GPCR expression by human islets may inform direction on novel GPCR targets...
August 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28807483/the-potential-efficacy-of-gabab-antagonists-in-depression
#15
REVIEW
Robert C Alexander
Evidence for the potential utility of GABAB antagonists has been assembled from a variety of sources, including clinical experience with the GABAB agonist baclofen, murine genetic GABAB knock-outs, rodent studies of GABAB receptor expression and function following treatment with antidepressant therapies, animal models of depression, and some functional and post mortem data from human subjects. Definitive testing of GABAB antagonists in depression, however, still awaits the development of potent, selective and brain-penetrant compounds for human testing...
August 11, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28806581/engineered-systems-for-therapeutic-angiogenesis
#16
REVIEW
Shane Browne, Abhay Pandit
Ischemic disease caused by insufficient blood supply leads to a lack of oxygen and nutrients and a build-up of waste products in the affected tissue. Therapeutic angiogenesis, as a means to enhance perfusion of tissues with an inadequate blood supply, holds great promise for the treatment of ischemic disease. A wide range of factors that play a key role in physiological angiogenesis have been identified and trialed as pro-angiogenic agents. However, as yet pro-angiogenic treatments have failed to be translated clinically, owing to both lack of efficacy and safety concerns regarding the use of doses considerably larger than is typical present under physiological conditions...
August 11, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28803835/receptor-distribution-studies
#17
REVIEW
Renzo Carletti, Stefano Tacconi, Manolo Mugnaini, Philip Gerrard
Receptor distribution studies have played a key role in the characterization of receptor systems (e.g. GABAB, NMDA (GluNRs), and Neurokinin 1) and in generating hypotheses to exploit these systems as potential therapeutic targets. Distribution studies can provide important information on the potential role of candidate receptors in normal physiology/disease and alert for possible adverse effects of targeting the receptors. Moreover, they can provide valuable information relating to quantitative target engagement (e...
August 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28802874/targeting-gastrointestinal-nutrient-sensing-mechanisms-to-treat-obesity
#18
REVIEW
Mariana Norton, Kevin G Murphy
Gut hormones have important roles in the regulation of appetite and glucose homeostasis. Understanding how macronutrient sensing in the gastrointestinal tract modulates gut hormone release may reveal novel pharmacological or dietary approaches to metabolic disease. In this short review we discuss the mechanisms by which the gut senses macronutrients and the products of macronutrient digestion, and their putative utility in treating obesity and related conditions.
August 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28802873/gut-check-on-diabesity-leveraging-gut-mechanisms-for-the-treatment-of-type-2-diabetes-and-obesity
#19
REVIEW
Sarah Will, David C Hornigold, David J Baker, Matthew P Coghlan, Malcolm Mesquita, James L Trevaskis, Jacqueline Naylor
Gut hormones have long been understood to regulate food intake and metabolism. Bariatric surgery significantly elevates circulating gut hormone levels and is proven to affect acute remission of type 2 diabetes before any weight loss is observed. Subsequent weight loss is accrued over weeks to months but is sustained into the long term. Hence, there exists great enthusiasm to recapitulate these changes in gut hormones in the form of novel combination drugs for type 2 diabetes and obesity.
August 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28802779/pharmacological-aspects-of-closed-loop-insulin-delivery-for-type-1-diabetes
#20
REVIEW
Chukwuma Uduku, Nick Oliver
Insulin deficiency and impaired glucose homeostasis are hallmarks of type 1 diabetes. Since the discovery of insulin, pharmacological and clinical developments have endeavoured to replicate its endogenous pharmacokinetics (PK) and pharmacodynamics (PD). Closed loop insulin delivery systems operate as an artificial pancreas by making automated insulin dose adjustments based on real time continuous glucose monitoring. The increasing adoption of continuous insulin pump therapy and evolving technological advances have seen significant progress in the development of closed loop insulin delivery systems...
August 10, 2017: Current Opinion in Pharmacology
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