Nanocomposites of Layered Clays and graphene/graphene oxide for drug delivery

Layered double hydroxides (LDH) comprise a class of materials that can be either found as natural minerals or can be synthetically prepared. Their structure is composed of a mixture of divalent and trivalent metal cations, forming brucite-like layers, that are neutralized with anions in the interlayer gallery. They have unique physical and chemical characteristics such as: high surface area, large charge density, biocompatibility and exchange capacity. These have attracted attention to the LDHs as potential drug delivery vehicles. Graphene (G) has also attracted the attention to exceptional properties, such as huge surface area, charge density concentration, membrane permeability by piercing mechanism and many others, expanding its use to include biomedical applications, such as drug delivery. Moreover, the possibility of large scale production of exfoliated graphene oxide (GO) sheets from G offered a further opportunity for their use. GO has a high exposed oxygenated surface that allows loading of large number of drugs by different bonding interactions and is dispersible in water. Alendronate sodium is a water soluble nitrogen containing bisphosphonate (nBP) drug, that has low bioavailabilty (\u3c 1 %) due to its low epithelial permeability. It also exhibits gastrointestinal adverse effects. The objective of the work is to create a hybrid nanocomposite of Zn-Al LDH in its nitrate form with G/GO, (G/GO-Zn-Al-NO3 LDH), combining the properties of these structures: membrane permeability and large interacting surface of G or GO, the buffering effect and the capability of the LDH in storing and controlling the drug release. The hybrid nanocomposites incorporated 2% w/w of G or GO with two different M2+/M3+ ratios of LDH, 2:1 and 3:1. They were loaded with the drug by co-precipitation and ion exchange. The samples were characterized by XRD, FTIR, Zetasizer analyzer, and the amount of drug loaded and released were determined by UV/Vis spectroscopy, and the results were compared to those of drug-LDH controls. Samples that have show successful intercalation of the drug in bi-layered arrangement are: co-precipitation samples using M2+/M3+ ratio of 3:1 (drug-LDH, G/GO-LDH), and ion-exchange samples, that don’t incorporate G/GO (drug-LDH), prepared using either M2+/M3+ ratios of 2:1or 3:1. Their loading amounts ranged from 25.4 to 51 % w/w, and they exhibited a sustained release over 24 hours with a release percentages, ranging from 2.1% (1.07 mg) up to 4.2 % (1.52 mg). The other samples showed loading by surface adsorption on brucite-like layers of the LDH and the G or GO. They have drug loading amounts ranging, from 12.4 to 57.3 % w/w. This work demonstrated the potential of G/GO-Zn-Al LDH nanocomposites for sustained drug delivery

Self-organization skills and their relationship to school integration among high school students

The study aimed to reveal the relationship between self-organization skills with school integration among high school students, and the study sample consisted of (710) high school students, the male sample was (330) and the female sample was (380) in secondary schools in the southern governorates of Palestine, and the study used the self-organization scale. And the school integration scale and the study followed the descriptive approach, and the study concluded that the relative weight of the axis of self-organization skills was (74%) high, while the relative weight of the axis of school integration reached (76.8%), and there is a statistically significant relationship at the level of significance ( α ≥ 0.05) between self-organization skills and school integration, and there are statistically significant differences at the significance level (α ≤ 0.05) between the average grades of high school students on the self-organization skills scale, and the school integration scale for study variables (type - grade in the previous grade). Keywords: self-organization - school integration - high school students. DOI: 10.7176/RHSS/13-10-06 Publication date:May 31st 202

What is the epidemiology of medication errors, error-related adverse events and risk factors for errors in adults managed in community care contexts? A systematic review of the international literature

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.Objective To investigate the epidemiology of medication errors and error-related adverse events in adults in primary care, ambulatory care and patients’ homes. Design Systematic review. Data source Six international databases were searched for publications between 1 January 2006 and 31 December 2015. Data extraction and analysis Two researchers independently extracted data from eligible studies and assessed the quality of these using established instruments. Synthesis of data was informed by an appreciation of the medicines’ management process and the conceptual framework from the International Classification for Patient Safety. Results 60 studies met the inclusion criteria, of which 53 studies focused on medication errors, 3 on error-related adverse events and 4 on risk factors only. The prevalence of prescribing errors was reported in 46 studies: prevalence estimates ranged widely from 2% to 94%. Inappropriate prescribing was the most common type of error reported. Only one study reported the prevalence of monitoring errors, finding that incomplete therapeutic/safety laboratory-test monitoring occurred in 73% of patients. The incidence of preventable adverse drug events (ADEs) was estimated as 15/1000 person-years, the prevalence of drug–drug interaction-related adverse drug reactions as 7% and the prevalence of preventable ADE as 0.4%. A number of patient, healthcare professional and medication-related risk factors were identified, including the number of medications used by the patient, increased patient age, the number of comorbidities, use of anticoagulants, cases where more than one physician was involved in patients’ care and care being provided by family physicians/general practitioners. Conclusion A very wide variation in the medication error and error-related adverse events rates is reported in the studies, this reflecting heterogeneity in the populations studied, study designs employed and outcomes evaluated. This review has identified important limitations and discrepancies in the methodologies used and gaps in the literature on the epidemiology and outcomes of medication errors in community settings.Peer reviewe

Revisiting unexploited natural products in search of new antibacterial drug candidates: the case of the benzoisochromanequinone and dithiolopyrrolone classes

It has become vital to identify antibacterial drug candidates with novel modes of action to address the growing problem of antibiotic resistance. One way of rapidly accessing novel antibiotics is to revisit natural product classes that have previously been shown to possess antibacterial activity, but have never been clinically exploited. The recent introduction of the antibiotics daptomycin, retapamulin, and fidaxomicin to the clinic is a proof of concept that revisiting known of novel natural product scaffolds could achieve clinical benefit. In this thesis, the benzoisochromanequinone (BIQ) and dithiolopyrrolone (DTP) classes of natural products were revisited. In chapter three, the BIQ class actinorhodin was subject to a detailed biological characterization. γ-actinorhodin was found to possess several requisite properties of a useful antibacterial drug candidate; it possessed potent bactericidal anti-Gram-positive activity, which included activity against MRSA and VISA strains (MIC90 of 2 μg/ml), was found to exhibit selective toxicity against prokaryotes, and displayed low resistance potential in vitro. Mode of action studies showed that γ-actinorhodin acts on the bacterial membrane in a manner distinct from other membrane-perturbing agents in clinical use. Preliminary studies of safety and efficacy of γ-actinorhodin in vivo showed potential promise for treatment staphylococcal infection. In chapter four of this thesis, the DPT thiolutin was studied, with an emphasis on understanding its mode of antibacterial action. In E. coli, thiolutin demonstrated preferential inhibition of RNA synthesis in agreement with earlier studies. In S. aureus however, while potent bacteriostatic activity was noted, thiolutin showed an unusual profile in radiolabel incorporation experiments with no inhibitory effect on any macromolecular biosynthetic pathway. Genetic analysis of mutants resistant to thiolutin revealed mutations in the S.aureus thioredoxin and in E. coli glutaredoxin redox systems components suggesting the involvement of these systems in the reductive activation of thiolutin. Inhibition of E. coli transcription and translation could not be detected in vitro, even in the presence of reducing agent suggested that RNA polymerase is not the primary target of thiolutin. The finding from this study and recent publication (Chan et al. 2017) suggest that DTPs exerts their antibacterial activity via a novel mode of action. In summary, the findings of this study with thiolutin and γ-actinorhodin underscore the utility of revisiting unexploited natural product in the search for antibacterials with novel mode of action

An Energy Efficient Sleep/Wake up Routing Protocol for Wireless Sensor Networks

In recent years, wireless sensor networks (WSNs) have a rapid development and they take a lot of research attention because of their wide-range applications. A WSN consists of a large number of distributed sensor nodes. These nodes are often deployed in remote or hostile areas to monitor physical or environmental conditions where they send this data to a main location. The most critical parameter in WSNs is network lifetime, so an efficient routing protocol is essential to reduce the energy consumption and to increase the network lifetime. This paper proposes an energy-efficient chain-based cooperative routing protocol based on node sleep/wake-up mechanism for WSNs. We compare this protocol with two efficient protocols; LEACH and CBCCP using MATLAB. Simulation results show that the proposed algorithm achieves better performance and conserves more energy than the other two protocols

FLOATING RANITIDINE MICROPARTICULATES: DEVELOPMENT AND IN VITRO EVALUATION

Objective: Rapid and inconsistent gastrointestinal tract (GIT) transit could result in reduced drug efficiency and the need for frequent dose administration, which usually result in patients' incompliance. Ranitidine hydrochloride (RH), as a model drug is freely soluble, moisture sensitive drug with a short biological half-life (~2.5-3 h) and narrow absorption window in the initial part of the small intestine. The present study aimed to develop ranitidine floating multi-particulates (RFM) using melt granulation technique and investigation of the effect of lipids and additives on the physicochemical properties. Methods: RFM were prepared using Compritol® 888 ATO, glyceryl behenate, Cutina® HR, Cutina® GMS, hydrogenated castor oil, glyceryl monostearate, and beeswax as lipids and ethyl cellulose, Povidone® K 90 and Aerosil® 200 as release modifiers. The effect of the preparation method and additives, as well as storage for 6 mo at 40 °C, on floating and release characteristics were evaluated. Results: Size distribution indicated that the prepared formulations exhibited reasonably small floating micro particulates; more than 90% of the prepared microparticles were less than 710 µm. Hausner ratios and Carr's compressibility indices ranged from 1.17 to 1.29% and 14.54 to 22.4 %, respectively, and the angle of repose values was ≤40 °, indicating good flow properties. RFM containing Compritol® showed a relatively higher release properties compared to hydrogenated castor oil. Increasing the proportion of the fatty component was accompanied by retardation in RH release. The tested additives (PVP, ethyl cellulose, Aerosil®) resulted in different degrees of retardation of drug release. The percent-floating of RFM was almost 100% in all formulations with the exception of formulations prepared using glyceryl monostearate. FT-IR and DSC studies indicated the compatibility of the excipients with RH. Stability results revealed an insignificant change in RFM properties over 6 mo. Conclusion: The prepared microparticles exhibited optimum particle size, good compressibility, and flow properties. RFM containing Compritol® showed a relatively higher release properties compared to hydrogenated castor oil. Increasing the proportion of the fatty component was accompanied by retardation in RH release. The percent-floating of RFM was almost 100% in most formulations. FT-IR and DSC indicated good compatibility of the excipients with RH and insignificant change in RFM properties over 6 mo's storage

Determination of dimenhydrinate and cinnarizine in combined dosage form in presence of cinnarizine impurity

Three accurate, sensitive and time saving spectrophotometric methods have been developed and validated for determination of mixture of dimenhydrinate (DMH) and cinnarizine (CIN) in presence of cinnarizine impurity (1-(diphenylmethyl)piperazine) (IMP). In method A; dimenhydrinate was determined by measuring 1D amplitudes at 292.0 nm while cinnarizine and its impurity were determined by 1DD method at 256.2 and 219.6 nm, respectively, using standard spectrum of 20 µg/mL of dimenhydrinate as a divisor. Method B depends on dividing spectrum of ternary mixture by standard spectrum of 20 µg/mL of dimenhydrinate and then cinnarizine and its impurity were determined in the obtained ratio spectrum by ratio difference method using the difference between 219.0 and 237.2 nm and between 230.0 and 264.0 nm, respectively. On the other hand dimenhydrinate could be determined by dividing spectrum of ternary mixture by standard spectrum of 20 µg/mL of cinnarizine and then it were determined at the obtained ratio spectrum by ratio difference method using the difference between 216.8 and 232.8 nm. Method C is the mean cantering of ratio spectra method (MCR) where the amplitudes at 234.8, 240.0 and 233.6 nm in the second mean centering ratio spectra were used for determination of dimenhydrinate, cinnarizine and its impurity, respectively. The developed methods were validated according to ICH guidelines regarding good accuracy and precision, and they were successfully applied to pharmaceutical formulation and laboratory prepared mixtures. The results were statistically compared with those obtained by reported method and no significant difference was found

CitySim: A Drone-Based Vehicle Trajectory Dataset for Safety Oriented Research and Digital Twins

The development of safety-oriented research and applications requires fine-grain vehicle trajectories that not only have high accuracy, but also capture substantial safety-critical events. However, it would be challenging to satisfy both these requirements using the available vehicle trajectory datasets do not have the capacity to satisfy both.This paper introduces the CitySim dataset that has the core objective of facilitating safety-oriented research and applications. CitySim has vehicle trajectories extracted from 1140 minutes of drone videos recorded at 12 locations. It covers a variety of road geometries including freeway basic segments, signalized intersections, stop-controlled intersections, and control-free intersections. CitySim was generated through a five-step procedure that ensured trajectory accuracy. The five-step procedure included video stabilization, object filtering, multi-video stitching, object detection and tracking, and enhanced error filtering. Furthermore, CitySim provides the rotated bounding box information of a vehicle, which was demonstrated to improve safety evaluations. Compared with other video-based critical events, including cut-in, merge, and diverge events, which were validated by distributions of both minimum time-to-collision and minimum post-encroachment time. In addition, CitySim had the capability to facilitate digital-twin-related research by providing relevant assets, such as the recording locations' three-dimensional base maps and signal timings.Comment: Transportation Research Record (2023