The continuums of impairment in vascular reactivity across the spectrum of cardiometabolic health: a systematic review and network meta-analysis

This study aimed to assess, for the first time, the change in vascular reactivity across the full spectrum of cardiometabolic health. Systematic searches were conducted in MEDLINE and EMBASE databases from their inception to March 13, 2017, including studies that assessed basal vascular reactivity in two or more of the following health groups (aged ≥18 years old): healthy, overweight, obesity, impaired glucose tolerance, metabolic syndrome, or type 2 diabetes with or without complications. Direct and indirect comparisons of vascular reactivity were combined using a network meta-analysis. Comparing data from 193 articles (7226 healthy subjects and 19344 patients), the network meta-analyses revealed a progressive impairment in vascular reactivity (flow-mediated dilation data) from the clinical onset of an overweight status (-0.41%, 95% CI, -0.98 to 0.15) through to the development of vascular complications in those with type 2 diabetes (-4.26%, 95% CI, -4.97 to -3.54). Meta-regressions revealed that for every 1 mmol/l increase in fasting blood glucose concentration, flow-mediated dilation decreased by 0.52%. Acknowledging that the time course of disease may vary between patients, this study demonstrates multiple continuums of vascular dysfunction where the severity of impairment in vascular reactivity progressively increases throughout the pathogenesis of obesity and/or insulin resistance, providing information that is important to enhancing the timing and effectiveness of strategies that aim to improve cardiovascular outcomes.Jordan Loader, Charles Khouri, Frances Taylor, Simon Stewart, Christian Lorenzen, Jean, Luc Cracowski, Guillaume Walther, Matthieu Rousti

Oral Fast and Topical Controlled Ketoprofen Release Through Supercritical Fluids Based Processes

Ketoprofen (KET) is a non-steroidal anti-inflammatory drug (NSAID) widely used for different phlogistic diseases of rheumatoid and non-rheumatoid origin. When a fast release is required, KET is orally administered in form of capsules, tablets or granulates. In this case, due to KET poor solubility in water, large drug doses with consequent side effects, mainly gastrointestinal one are required. KET bioavailability can be enhanced through its coprecipitation with a hydrophilic carrier, such as polyvinylpyrrolidone (PVP). Another way to reduce the dosing frequency and avoid gastrointestinal irritation is the transdermal drug delivery with a controlled release. In this work, two different supercritical carbon dioxide (scCO2) based processes were used to modify KET dissolution rate: the supercritical antisolvent technique to coprecipitate PVP and KET in form of controlled dimensions microparticles for an oral delivery, and the supercritical adsorption to impregnate KET in alginate aerogel for a topical delivery. In the case of oral KET, composite spherical microparticles with controlled diameters were successfully produced, leading to a faster NSAID dissolution rate than unprocessed KET. In the case of topical KET, alginate aerogel was successfully impregnated with KET; it promotes a controlled release, suitable for transdermal anti-inflammatory patches, reducing frequency of administration and side effects. Supercritical techniques allow to obtain a fast or controlled release of the NSAID, according to the specific therapy desired

pH-Sensitive Hydrogels Based on (Meth)Acrylates and Itaconic Acid

Novel hydrogels based on 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA) and different poly (alkylene glycol) (meth)acrylates (PAGM) (P(HEMA/IA/PAGM)) were synthesized. We investigated the influence of different PAGM components, with acrylic or methacrylic acid residues in the main chain and ethylene glycol (EG) and/or propylene glycol (PG) units in pendant chains of varying length, on the nature and inherent properties of P(HEMA/IA/PAGM) copolymeric hydrogels. Swelling studies revealed pH sensitive behavior of P(HEMA/IA/PAGM) samples. Hydrogel structure and morphology were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), which confirmed their chemical structure and differences in pore size. The shear modulus values for P(HEMA/IA/PAGM) hydrogels were close to that of PHEMA, but slightly lower than the value for P(HEMA/IA). Cephalexin (CEX) drug release profiles from P(HEMA/IA/PAGM) samples showed a marked dependence on the PAGM component. The presence of IA also influenced the release rate of CEX, leading to a faster release when IA was combined with the more hydrophilic PAGM component. An in vitro assay of P(HEMA/IA/PAGM) cytotoxicity showed good cell viability. The results obtained indicate that P(HEMA/IA/PAGM) hydrogel properties were significantly dependent on the PAGM component, meaning that the type of side chains can be used to tune the characteristics of such biomaterials. These properties make P(HEMA/IA/PAGM) copolymeric hydrogels applicable in biomedical and biotechnological fields and controlled drug delivery