Synchronized and controlled release of metformin hydrochloride/glipizide from elementary osmotic delivery

The combination of metformin hydrochloride (MTF) and glipizide (GLZ) is second-line medication for diabetes mellitus type 2 (DMT2). In the present study, elementary osmotic pump(EOP)tablet is designed to deliver the combination of MTF and GLZ in a sustained and synchronized manner. By analyzing different variables of the formulation, sodium hydrogen carbonate is introduced as pH modifier to improve the release of GLZ, while ethyl cellulose acts as release retardant to reduce the burst release phase of MTF. A two factor, three level face-centered central composite design (FCCD) is applied to investigate the impact of different factors on drug release profile. Compared with conventional tablets, the elementary osmotic pump (EOP) tablet demonstrates a controlled release behavior with relative bioavailability of 99.2% for MTF and 99.3% for GLZ. Data also shows EOP tablet is able to release MTF and GLZ in a synchronized and sustained manner both in vitro and in vivo

Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel

A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception.

A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol

BACKGROUND: Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia.

METHODS/DESIGN: This is a randomised controlled trial of calcium channel blockade with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks.

DISCUSSION: There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions.

A randomized controlled trial of an early-intervention, computer-based literacy program to boost phonological skills in 4- to 6-year-old children

Background: Many school-based interventions are being delivered in the absence of evidence of effectiveness (Snowling & Hulme, 2011, Br. J. Educ. Psychol., 81, 1).Aim: This study sought to address this oversight by evaluating the effectiveness of the commonly used the Lexia Reading Core5 intervention, with 4- to 6-year-old pupils in Northern Ireland.Sample: A total of 126 primary school pupils in year 1 and year 2 were screened on the Phonological Assessment Battery 2nd Edition (PhAB-2). Children were recruited from the equivalent year groups to Reception and Year 1 in England and Wales, and Pre-kindergarten and Kindergarten in North America.
Methods: A total of 98 below-average pupils were randomized (T0) to either an 8-week block (inline image = 647.51 min, SD = 158.21) of daily access to Lexia Reading Core5 (n = 49) or a waiting-list control group (n = 49). Assessment of phonological skills was completed at post-intervention (T1) and at 2-month follow-up (T2) for the intervention group only.
Results: Analysis of covariance which controlled for baseline scores found that the Lexia Reading Core5 intervention group made significantly greater gains in blending, F(1, 95) = 6.50, p = .012, partial η2 = .064 (small effect size) and non-word reading, F(1, 95) = 7.20, p = .009, partial η2 = .070 (small effect size). Analysis of the 2-month follow-up of the intervention group found that all group treatment gains were maintained. However, improvements were not uniform among the intervention group with 35% failing to make progress despite access to support. Post-hoc analysis revealed that higher T0 phonological working memory scores predicted improvements made in phonological skills.
Conclusions: An early-intervention, computer-based literacy program can be effective in boosting the phonological skills of 4- to 6-year-olds, particularly if these literacy difficulties are not linked to phonological working memory deficits.

Toward controlled growth of helicity-specific carbon nanotubes

The underlying mechanisms for the nucleation of carbon nanotubes as well as their helicity, remain elusive. Here, using van der Waals dispersion force calculations implemented within density functional theory, we study the cap formation, believed to be responsible for the chirality of surface-catalyzed carbon nanotubes. We find the energetics associated with growth along different facets to be independent of the surface orientation and that the growth across an edge along the axis of the metal particle leads to a perfect honeycomb lattice in a curved geometry. The formation of defects in the graphene matrix, which bend the carbon plane, requires that two or more graphene embryos with significantly different growth axis merge. Such scenario is only possible at the front- or back-end of the metal particle where growth symmetry is broken. The graphene embryos reconstruct their hexagonal structure into pentagons, heptagons, and octagons counterpart to accommodate the tube curvature.

Endonuclease Controlled Aggregation of Gold Nanoparticles for the Ultrasensitive Detection of Pathogenic Bacterial DNA

The development of an ultrasensitive biosensor for the low-cost and on-site detection of pathogenic DNA could transform detection capabilities within food safety, environmental monitoring and clinical diagnosis. Herein, we present an innovative approach exploiting endonuclease-controlled aggregation of plasmonic gold nanoparticles (AuNPs) for label-free and ultrasensitive detection of bacterial DNA. The method utilizes RNA-functionalized AuNPs which form DNA-RNA heteroduplex structures through specific hybridization with target DNA. Once formed, the DNA-RNA heteroduplex is susceptible to RNAse H enzymatic cleavage of the RNA probe, allowing the target DNA to liberate and hybridize with another RNA probe. This continuously happens until all of the RNA probes are cleaved, leaving the nanoparticles unprotected and thus aggregated upon exposure to a high electrolytic medium. The assay is ultrasensitive, allowing the detection of target DNA at femtomolar level by simple spectroscopic analysis (40.7 fM and 2.45 fM as measured by UV-vis and dynamic light scattering (DLS), respectively). The target DNA spiked food matrix (chicken meat) is also successfully detected at a concentration of 1.2 pM (by UV-vis) or 18.0 fM (by DLS). In addition to the ultra-high sensitivity, the total analysis time of the assay is less than 3 hours, thus demonstrating its practicality for food analysis.

Intrinsically flexible electronic materials for smart device applications

A novel method to fabricate chemically linked conducting polymer–biopolymer composites that are intrinsically flexible and conducting for functional electrode applications is presented. Polypyrrole was synthesised in situ during the cellulose regeneration process using the 1-butyl-3-methylimidazolium chloride ionic liquid as a solvent medium. The obtained polypyrrole–cellulose composite was chemically blended and showed flexible polymer properties while retaining the electronic properties of a conducting polymer. Addition of an ionic liquid such as trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide, enhanced the flexibility of the composite. The functional application of these materials in the electrochemically controlled release of a model drug has been demonstrated. This strategy opens up a new design for a wide spectrum of materials for smart electronic device applications wherein the functionality of doping and de-doping of conducting polymers is retained and their processability issue is addressed by exploiting an ionic liquid route.