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1.
Recent Strategies in Resveratrol Delivery Systems.
Machado, ND, Fernández, MA, Díaz, DD
ChemPlusChem. 2019;(7):951-973
Abstract
Resveratrol, a natural polyphenolic stilbenoid widely found in grapes and wines, displays beneficial properties such as cardio-protective, antioxidant and anti-inflammatory activities. Trans-resveratrol (RSV) is the most bioactive and more abundant stereoisomer found in nature. Despite the positive properties of RSV, there are various factors that limit its effectiveness, including low aqueous solubility, low oral bioavailability and chemical instability. During the last years, an increasing number of strategies such as nano and micro encapsulation have been developed in order to overcome these limitations and enhance the use of RSV in nutritional and pharmaceutical applications. This Review summarizes the advances and main properties of several RSV carriers and delivery systems reported during the last 5 years.
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2.
Posterior segment drug delivery for the treatment of exudative age-related macular degeneration and diabetic macular oedema.
Wong, CW, Wong, TT
The British journal of ophthalmology. 2019;(10):1356-1360
Abstract
Inhibitors of vascular endothelial growth factors are used to treat a myriad of retinal conditions, including exudative age-related macular degeneration (AMD), diabetic macular oedema (DME) and diabetic retinopathy. Although effective, long-term efficacy is limited by the need for frequent and invasive intravitreal injections. The quest for sustained action therapeutics that can be delivered to target tissue in the least invasive manner is an arduous endeavour that has ended in premature failure for several technologies in Phase II or III trials. Nevertheless, there have been promising preclinical studies, and more are on the horizon: port delivery systems for the treatment of exudative AMD have entered Phase III trials and a wide array of preclinical studies have demonstrated the potential for nanoparticles, such as liposomes, dendrimers and cell penetrating peptides to deliver therapeutics into the posterior segment via minimally invasive routes. In this review, we discuss the challenges posed by ocular barriers for drug penetration and present the recent advancements of the most pertinent drug delivery platforms with a focus on the treatment of exudative AMD and DME.
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3.
Click Chemistry as a Tool for Cell Engineering and Drug Delivery.
Takayama, Y, Kusamori, K, Nishikawa, M
Molecules (Basel, Switzerland). 2019;(1)
Abstract
Click chemistry has great potential for use in binding between nucleic acids, lipids, proteins, and other molecules, and has been used in many research fields because of its beneficial characteristics, including high yield, high specificity, and simplicity. The recent development of copper-free and less cytotoxic click chemistry reactions has allowed for the application of click chemistry to the field of medicine. Moreover, metabolic glycoengineering allows for the direct modification of living cells with substrates for click chemistry either in vitro or in vivo. As such, click chemistry has become a powerful tool for cell transplantation and drug delivery. In this review, we describe some applications of click chemistry for cell engineering in cell transplantation and for drug delivery in the diagnosis and treatment of diseases.
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4.
Basic principles of drug delivery systems - the case of paclitaxel.
Ezrahi, S, Aserin, A, Garti, N
Advances in colloid and interface science. 2019;:95-130
Abstract
Cancer is the second cause of death worldwide, exceeded only by cardiovascular diseases. The prevalent treatment currently used against metastatic cancer is chemotherapy. Among the most studied drugs that inhibit neoplastic cells from acquiring unlimited replicative ability (a hallmark of cancer) are the taxanes. They operate via a unique molecular mechanism affecting mitosis. In this review, we show this mechanism for one of them, paclitaxel, and for other (non-taxanes) anti-mitotic drugs. However, the use of paclitaxel is seriously limited (its bioavailability is <10%) due to several long-standing challenges: its poor water solubility (0.3 μg/mL), its being a substrate for the efflux multidrug transporter P-gp, and, in the case of oral delivery, its first-pass metabolism by certain enzymes. Adequate delivery methods are therefore required to enhance the anti-tumor activity of paclitaxel. Thus, we have also reviewed drug delivery strategies in light of the various physical, chemical, and enzymatic obstacles facing the (especially oral) delivery of drugs in general and paclitaxel in particular. Among the powerful and versatile platforms that have been developed and achieved unprecedented opportunities as drug carriers, microemulsions might have great potential for this aim. This is due to properties such as thermodynamic stability (leading to long shelf-life), increased drug solubilization, and ease of preparation and administration. In this review, we define microemulsions and nanoemulsions, analyze their pertinent properties, and review the results of several drug delivery carriers based on these systems.
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5.
Opening of ATP-sensitive potassium channels causes migraine attacks: a new target for the treatment of migraine.
Al-Karagholi, MA, Hansen, JM, Guo, S, Olesen, J, Ashina, M
Brain : a journal of neurology. 2019;(9):2644-2654
Abstract
Migraine is one of the most disabling and prevalent of all disorders. To improve understanding of migraine mechanisms and to suggest a new therapeutic target, we investigated whether opening of ATP-sensitive potassium channels (KATP) would cause migraine attacks. In this randomized, double-blind, placebo-controlled, crossover study, 16 patients aged 18-49 years with one to five migraine attacks a month were randomly allocated to receive an infusion of 0.05 mg/min KATP channel opener levcromakalim and placebo on two different days (ClinicalTrials.gov number, NCT03228355). The primary endpoints were the difference in incidence of migraine attacks, headaches and the difference in area under the curve (AUC) for headache intensity scores (0-12 h) and for middle cerebral artery blood flow velocity (0-2 h) between levcromakalim and placebo. Between 24 May 2017 and 23 November 2017, 16 patients randomly received levcromakalim and placebo on two different days. Sixteen patients (100%) developed migraine attacks after levcromakalim compared with one patient (6%) after placebo (P = 0.0001); the difference of incidence is 94% [95% confidence interval (CI) 78-100%]. The incidence of headache over the 12 h observation period was higher but not significant after levcromakalim (n = 16) than after placebo (n = 7) (P = 0.016) (95% CI 16-71%). The AUC for headache intensity was significantly larger after levcromakalim compared to placebo (AUC0-12h, P < 0.0001). There was no change in mean middle cerebral artery blood flow velocity after levcromakalim compared to placebo (AUC0-2hP = 0.46). Opening of KATP channels caused migraine attacks in all patients. This suggests a crucial role of these channels in migraine pathophysiology and that KATP channel blockers could be potential targets for novel drugs for migraine.
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6.
Nanostructured cochleates: a multi-layered platform for cellular transportation of therapeutics.
Shende, P, Khair, R, Gaud, RS
Drug development and industrial pharmacy. 2019;(6):869-881
Abstract
Among lipid-based nanocarriers, multi-layered cochleates emerge as a novel delivery system because of prevention of oxidation of hydrophobic and hydrophilic drugs, enhancement in permeability, and reduction in dose of drugs. It also improves oral bioavailability and increases the safety of a drug by targeting at a specific site with less side effects. Nanostructured cochleates are used as a carrier for the delivery of water-insoluble or hydrophobic drugs of anticancer, antiviral and anti-inflammatory action. This review article focuses on different methods for preparation of cochleates, mechanism of formation of cochleates, mechanism of action like cochleate undergoes macrophagic endocytosis and release the drug into the systemic circulation by acting on membrane proteins, phospholipids, and receptors. Advanced methods such as calcium-substituted and β-cyclodextrin-based cochleates, novel techniques include microfluidic and modified trapping method. Cochleates showed enhancement in oral bioavailability of amphotericin B, delivery of factor VII, oral mucosal vaccine adjuvant-delivery system, and delivery of volatile oil. In near future, cochleate will be one of the interesting delivery systems to overcome the stability and encapsulation efficiency issues associated with liposomes. The current limiting factors for commercial preparation of cochleates involve high cost of manufacturing, lack of standardization, and specialized equipments.
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7.
Nanotherapy Targeting the Tumor Microenvironment.
Gong, BS, Wang, R, Xu, HX, Miao, MY, Yao, ZZ
Current cancer drug targets. 2019;(7):525-533
Abstract
Cancer is characterized by high mortality and low curability. Recent studies have shown that the mechanism of tumor resistance involves not only endogenous changes to tumor cells, but also to the tumor microenvironment (TME), which provides the necessary conditions for the growth, invasion, and metastasis of cancer cells, akin to Stephen Paget's hypothesis of "seed and soil." Hence, the TME is a significant target for cancer therapy via nanoparticles, which can carry different kinds of drugs targeting different types or stages of tumors. The key step of nanotherapy is the achievement of accurate active or passive targeting to trigger drugs precisely at tumor cells, with less toxicity and fewer side effects. With deepened understanding of the tumor microenvironment and rapid development of the nanomaterial industry, the mechanisms of nanotherapy could be individualized according to the specific TME characteristics, including low pH, cancer-associated fibroblasts (CAFs), and increased expression of metalloproteinase. However, some abnormal features of the TME limit drugs from reaching all tumor cells in lethal concentrations, and the characteristics of tumors vary in numerous ways, resulting in great challenges for the clinical application of nanotherapy. In this review, we discuss the essential role of the tumor microenvironment in the genesis and development of tumors, as well as the measures required to improve the therapeutic effects of tumor microenvironment-targeting nanoparticles and ways to reduce damage to normal tissue.
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8.
An Overview on Genistein and its Various Formulations.
Jaiswal, N, Akhtar, J, Singh, SP, , , Ahsan, F
Drug research. 2019;(6):305-313
Abstract
Genistein is the natural isoflavone and a phytoestrogen with a broad range of pharmacological properties, such as tyrosine and topoisomerase inhibition. It also induces apoptosis and cell proliferation inhibition, differentiates cancer cells. Added health benefits include the reduction of osteoporosis by suppressing osteoclasts and lymphocyte functions, decreased the risk of cardiovascular attacks and relieved postmenopausal problems. Genistein traditionally used in Chinese and Ayurvedic medicine and are found to be associated with lower risk of breast, prostate and lung cancer. Numerous factors comprising genetic, epigenetic and transcriptomic alterations are evidenced to be responsible for breast, prostate and lung cancer. In present review, an overview on genistein, the various analytical methods and drug delivery approaches to determine genistein in the formulations are discussed. It may help to develop novel formulations with better solubility and bioavailability of genistein. The tumor cell scan may be targeted to form a stable genistein formulation.
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9.
Anaphylaxis management in Australian schools: Review of guidelines and adrenaline autoinjector use.
Vale, S, Netting, MJ, Ford, LS, Tyquin, B, McWilliam, V, Campbell, DE
Journal of paediatrics and child health. 2019;(2):143-151
Abstract
Food allergy and anaphylaxis is increasing in Australian children, and anaphylaxis is relatively common in Australian schools. This review aims to provide an overview of current policies and practices for anaphylaxis management in Australian schools, including approaches to risk mitigation and anaphylaxis training. We reviewed literature related to anaphylaxis training in the school setting published between 2010 and 2018. Current anaphylaxis policies/guidelines were obtained from Australian education and health departments, and reports of suspected anaphylaxis and adrenaline autoinjector (AAI) use for 2016-2017 were obtained from education departments where available. Our review of policies/guidelines across Australian jurisdictions indicates inconsistent approaches to anaphylaxis management training. Almost half of Australian school anaphylaxis events required a general-use AAI, administered to students not identified as at risk of anaphylaxis. Development of clear, evidence-based, consistent guidelines related to anaphylaxis management and training in the school setting is imperative to minimise risk.
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10.
A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects.
Knaub, K, Sartorius, T, Dharsono, T, Wacker, R, Wilhelm, M, Schön, C
Molecules (Basel, Switzerland). 2019;(16)
Abstract
Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa, shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation. Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h). Subgroup analysis demonstrated a higher bioavailability in women compared to men. This difference was seen for MCT-CBD while SEDDS-CBD mitigated this gender effect. Overall, SEDDS-CBD showed a significant improvement for all determined pharmacokinetic parameters: increased CBD plasma values (Cmax), favorably enhanced bioavailability (AUC) and fast absorption (Tmax). No safety concerns were noted following either administration.