pH-Responsive Hydrogel Beads Based on Alginate, k-Carrageenan and Poloxamer for enhanced curcumin, natural bioactive compound, encapsulation and controlled release efficiency

Polyphenolic compounds are used for treating various diseases due to their antioxidant and anticancer properties. However, utilization of hydrophobic compounds is limited due to their low bioavailability. In order to achieve a greater application of hydrophobic bioactive compounds, hydrogel beads based on biopolymers can be used as carriers for their enhanced incorporation and controlled delivery. In this study, beads based on the biopolymers-k-carrageenan, sodium alginate and poloxamer 407 were prepared for encapsulation of curcumin. The prepared beads were characterized using IR, SEM, TGA and DSC. The curcumin encapsulation efficiency in the developed beads was 95.74 +/- 2.24%. The release kinetics of the curcumin was monitored in systems that simulate the oral delivery (pH 1.2 and 7.4) of curcumin. The drug release profiles of the prepared beads with curcumin indicated that the curcumin release was significantly increased compared with the dissolution of curcumin itself. The cumulative release of curcumin from the beads was achieved within 24 h, with a final release rate of 12.07% (gastric fluid) as well as 81.93% (intestinal fluid). Both the in vitro and in vivo studies showed that new hydrogel beads based on carbohydrates and poloxamer improved curcumin’s bioavailability, and they can be used as powerful carriers for the oral delivery of different hydrophobic nutraceuticals

Curcumin and diclofenac therapeutic efficacy enhancement applying transdermal hydrogel polymer films, based on carrageenan, alginate and poloxamer

Films based on carrageenan, alginate and poloxamer 407 have been formulated with the main aim to apply prepared formulations in wound healing process. The formulated films were loaded with diclofenac, an anti-inflammatory drug, as well as diclofenac and curcumin, as multipurpose drug, in order to enhance encapsulation and achieve controlled release of these low bioavailable compounds. The obtained data demonstrated improved drugs bioavailability (encapsulation efficiency higher than 90%), with achieved high, cumulative in vitro release percentages (90.10% for diclofenac; 89.85% for curcumin and 95.61% for diclofenac in mixture-incorporated films).. The results obtained using theoretical models suggested that curcumin establish stronger, primarily dispersion interactions with carrier, in comparison with diclofenac. Curcumin and diclofenac-loaded films showed a great antibacterial activity against Gram-positive bacteria strains (Bacillus subtilis and Staphylococcus aureus, inhibition zone 16.67 mm and 13.67 mm, respectively), and in vitro and in vivo studies indicated that curcumin- and diclofenac-incorporated polymer films have a great tendency, as a new transdermal dressing, to heal wounds, because diclofenac can target the inflammatory phase and reduce pain, whereas curcumin can enhance and promote wound healing process

The von Willebrand factor A-1 domain binding aptamer BT200 elevates plasma levels of von Willebrand factor and factor VIII: a first-in-human trial

Von Willebrand factor (VWF) and factor VIII (FVIII) circulate in a noncovalent complex in blood and promote primary hemostasis and clotting, respectively. A new VWF A1-domain binding aptamer, BT200, demonstrated good subcutaneous bioavailability and a long half-life in non-human primates. This first-in-human, randomized, placebo-controlled, doubleblind trial tested the hypothesis that BT200 is well tolerated and has favorable pharmacokinetic and pharmacodynamic effects in 112 volunteers. Participants received one of the following: a single ascending dose of BT200 (0.18-48 mg) subcutaneously, an intravenous dose, BT200 with concomitant desmopressin or multiple doses. Pharmacokinetics were characterized, and the pharmacodynamic effects were measured by VWF levels, FVIII clotting activity, ristocetin-induced aggregation, platelet function under high shear rates, and thrombin generation. The mean half-lives ranged from 7-12 days and subcutaneous bioavailability increased dose-dependently exceeding 55% for doses of 6-48 mg. By blocking free A1 domains, BT200 dose-dependently decreased ristocetin-induced aggregation, and prolonged collagen-adenosine diphosphate and shear-induced platelet plug formation times. However, BT200 also increased VWF antigen and FVIII levels 4-fold (P<0.001), without increasing VWF propeptide levels, indicating decreased VWF/FVIII clearance. This, in turn, increased thrombin generation and accelerated clotting. Desmopressin-induced VWF/FVIII release had additive effects on a background of BT200. Tolerability and safety were generally good, but exaggerated pharmacology was seen at saturating doses. This trial identified a novel mechanism of action for BT200: BT200 dose-dependently increases VWF/FVIII by prolonging half-life at doses well below those which inhibit VWF-mediated platelet function. This novel property can be exploited therapeutically to enhance hemostasis in congenital bleeding disorders

Atherosclerosis / Von Willebrand factor antigen levels predict major adverse cardiovascular events in patients with carotid stenosis of the ICARAS study

Background and aims Von Willebrand factor (VWF) plays an important role in thrombogenesis and mediates platelet adhesion particularly under high shear stress. Such conditions are generally found in stenotic arteries and can eventually cause myocardial infarction or stroke. We aimed to study whether levels of VWF antigen (VWF:Ag) predict future major adverse cardiovascular events (MACE) in patients suffering from carotid artery stenosis. Methods Patients with atherosclerotic carotid artery disease defined by the presence of nonstenotic plaques or any degree of carotid stenosis were prospectively enrolled. Concentrations of VWF were measured by enzyme immunoassay. Results VWF:Ag levels were more stable after 4 freeze-thaw cycles, when compared to VWF activity, and we showed similar concentrations of VWF in citrated plasma and serum (4%). Levels of VWF:Ag predicted future cardiovascular events in 811 patients with carotid stenosis independent of known cardiovascular risk factors. Patients with VWF:Ag concentrations in the 4th quartile had a 44% event rate after an average 3-year follow up and a hazard ratio of 2.15 (95% confidence interval 1.463.16; p<0.001). Conclusions High concentrations of VWF:Ag predict major cardiovascular events in patients with carotid stenosis, and given their high event rate may be useful for risk stratification of such patients.(VLID)490120

The Wide-field Spectroscopic Telescope (WST) Science White Paper

The Wide-field Spectroscopic Telescope (WST) is proposed as a new facility dedicated to the efficient delivery of spectroscopic surveys. This white paper summarises the initial concept as well as the corresponding science cases. WST will feature simultaneous operation of a large field-of-view (3 sq. degree), a high multiplex (20,000) multi-object spectrograph (MOS) and a giant 3x3 sq. arcmin integral field spectrograph (IFS). In scientific capability these requirements place WST far ahead of existing and planned facilities. Given the current investment in deep imaging surveys and noting the diagnostic power of spectroscopy, WST will fill a crucial gap in astronomical capability and work synergistically with future ground and space-based facilities. This white paper shows that WST can address outstanding scientific questions in the areas of cosmology; galaxy assembly, evolution, and enrichment, including our own Milky Way; origin of stars and planets; time domain and multi-messenger astrophysics. WST's uniquely rich dataset will deliver unforeseen discoveries in many of these areas. The WST Science Team (already including more than 500 scientists worldwide) is open to the all astronomical community. To register in the WST Science Team please visit https://www.wstelescope.com/for-scientists/participat

The Wide-field Spectroscopic Telescope (WST) Science White Paper

The Wide-field Spectroscopic Telescope (WST) is proposed as a new facility dedicated to the efficient delivery of spectroscopic surveys. This white paper summarises the initial concept as well as the corresponding science cases. WST will feature simultaneous operation of a large field-of-view (3 sq. degree), a high multiplex (20,000) multi-object spectrograph (MOS) and a giant 3x3 sq. arcmin integral field spectrograph (IFS). In scientific capability these requirements place WST far ahead of existing and planned facilities. Given the current investment in deep imaging surveys and noting the diagnostic power of spectroscopy, WST will fill a crucial gap in astronomical capability and work synergistically with future ground and space-based facilities. This white paper shows that WST can address outstanding scientific questions in the areas of cosmology; galaxy assembly, evolution, and enrichment, including our own Milky Way; origin of stars and planets; time domain and multi-messenger astrophysics. WST's uniquely rich dataset will deliver unforeseen discoveries in many of these areas. The WST Science Team (already including more than 500 scientists worldwide) is open to the all astronomical community. To register in the WST Science Team please visit https://www.wstelescope.com/for-scientists/participat

The Wide-field Spectroscopic Telescope (WST) Science White Paper

The Wide-field Spectroscopic Telescope (WST) is proposed as a new facility dedicated to the efficient delivery of spectroscopic surveys. This white paper summarises the initial concept as well as the corresponding science cases. WST will feature simultaneous operation of a large field-of-view (3 sq. degree), a high multiplex (20,000) multi-object spectrograph (MOS) and a giant 3x3 sq. arcmin integral field spectrograph (IFS). In scientific capability these requirements place WST far ahead of existing and planned facilities. Given the current investment in deep imaging surveys and noting the diagnostic power of spectroscopy, WST will fill a crucial gap in astronomical capability and work synergistically with future ground and space-based facilities. This white paper shows that WST can address outstanding scientific questions in the areas of cosmology; galaxy assembly, evolution, and enrichment, including our own Milky Way; origin of stars and planets; time domain and multi-messenger astrophysics. WST's uniquely rich dataset will deliver unforeseen discoveries in many of these areas. The WST Science Team (already including more than 500 scientists worldwide) is open to the all astronomical community. To register in the WST Science Team please visit https://www.wstelescope.com/for-scientists/participat