Characterization of nanochannel delivery membrane systems for the sustained release of resveratrol and atorvastatin: new perspectives on promoting heart health

Novel drug delivery systems capable of continuous sustained release of therapeutics have been studied extensively for use in the prevention and management of chronic diseases. The use of these systems holds promise as a means to achieve higher patient compliance while improving therapeutic index and reducing systemic toxicity. In this work, an implantable nanochannel drug delivery system (nDS) is characterized and evaluated for the long-term sustained release of atorvastatin (ATS) and trans-resveratrol (t-RES), compounds with a proven role in managing atherogenic dyslipidemia and promoting cardioprotection. The primary mediators of drug release in the nDS are nanofluidic membranes with hundreds of thousands of nanochannels (up to 100,000/mm²) that attain zero-order release kinetics by exploiting nanoconfinement and molecule-to-surface interactions that dominate diffusive transport at the nanoscale. These membranes were characterized using gas flow analysis, acetone diffusion, and scanning and transmission electron microscopy (SEM, TEM). The surface properties of the dielectric materials lining the nanochannels, SiO₂ and low-stress silicon nitride, were further investigated using surface charge analysis. Continuous, sustained in vitro release for both ATS and t-RES was established for durations exceeding 1 month. Finally, the influence of the membranes on cell viability was assessed using human microvascular endothelial cells. Morphology changes and adhesion to the surface were analyzed using SEM, while an MTT proliferation assay was used to determine the cell viability. The nanochannel delivery approach, here demonstrated in vitro, not only possesses all requirements for large-scale high-yield industrial fabrication, but also presents the key components for a rapid clinical translation as an implantable delivery system for the sustained administration of cardioprotectants.     

HRMAS NMR spectroscopy combined with chemometrics as an alternative analytical tool to control cigarette authenticity

In this paper, we present for the first time the use of high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy combined with chemometrics as an alternative tool for the characterization of tobacco products from different commercial international brands as well as for the identification of counterfeits. Although cigarette filling is a very complex chemical mixture, we were able to discriminate between dark, bright, and additive-free cigarette blends belonging to six different filter-cigarette brands, commercially available, using an approach for which no extraction procedure is required. Second, we focused our study on a specific worldwide-distributed brand for which established counterfeits were available. We discriminated those from their genuine counterparts with 100 % accuracy using unsupervised multivariate statistical analysis. The counterfeits that we analyzed showed a higher amount of nicotine and solanesol and a lower content of sugars, all endogenous tobacco leaf metabolites. This preliminary study demonstrates the great potential of HRMAS NMR spectroscopy to help in controlling cigarette authenticity.

Acid–Base Properties, Solubility, Activity Coefficients and Na+ Ion Pair Formation of Complexons in NaCl(aq) at Different Ionic Strengths

The protonation constants and solubilities of three complexons [ethylenediamine-N,N′-disuccinic acid (EDDS), ethylene glycol bis(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA) and 1,2-cyclohexanediamine-N,N,N′,N′-tetraacetic acid (CDTA)] are reported in aqueous solutions of NaCl with different ionic strength values (0 ≤ I ≤ 4.8 mol·L^?1) and, in the case of CDTA, in (CH₃)₄NCl (0.1 ≤ I ≤ 2.7 mol·L^?1). The dependence on ionic strength of the protonation constants of these three complexons and four other complexons that were previously reported (NTA, EDTA, DTPA and TTHA), is analyzed in NaCl solution; the ionic strength influences quite strongly the protonation constants (as an example for CDTA, log₁₀ K ₁ = 10.54 and 9.25 at I = 0.1 and 1 mol·L^?1, respectively), while the effect of (CH₃)₄NCl concentration is lower. Based on the total solubility S ^T and the protonation constant data at different salt concentrations, the solubility of the neutral species S ⁰ and the solubility products K _S0 are obtained. The Setschenow coefficients k _m and the solubility values S ₀ ⁰ in pure water are also reported (S ₀ ⁰  = 0.55, 0.21 and 0.75 mmol·kg^?1 for EDDS, EGTA and CDTA, respectively). The dependence of the protonation constants on ionic strength is also interpreted in terms of ion pair formation, and the formation constants of Na⁺ species are reported.     

Titanium complexes bearing carbamato ligands as catalytic precursors for propylene polymerization reactions

This report describes propylene polymerization reactions with titanium complexes bearing carbamato ligands, Ti(O₂CNMe₂)Cl₂ ( I ) and Ti(O₂CR₂)₄ [R₂ = NMe₂ ( II ), NEt₂ ( III ) and ( IV )]. Combinations of these complexes and MAO form catalysts for the synthesis of atactic polypropylene, as confirmed by FT‐IR, DSC and ¹³C NMR analysis. Effects of main reaction parameters on the catalyst activity were studied including the type of complex, solvent, temperature, and the [Al]/[Ti] molar ratio. The highest activity was observed when chlorobenzene was used as a solvent and AlMe₃‐depleted MAO was employed as a cocatalyst. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4095–4102     

Active Sites of Dermatan Sulfate for Heparin Cofactor II. Isolation of a Nonasaccharide Fragment Containing Four Disaccharide Sequences [α-l-Iduronic Acid 2-O-Sulfate (1,3)-β-d-N-Acetylgalactosamine 4-Sulfate]

Abstract

The active site of dermatan sulfate (DS) for heparin cofactor II (HCII) was isolated in a fragment obtained by periodate oxidation, borohydride reduction, mild acid hydrolysis, and SE- and SAX-chromatography of beef mucosal and pig skin DS preparations. Characterization by mass spectrometry, one- and two-dimensional NMR spectroscopy, and HPLC analysis of disaccharides, obtained by exhaustive digestion with chondroitinase-ABC, indicates that the fragment has the prevalent structure 1, GalNAc-4SO₃-[IdoA-2SO₃-GalNAc-4SO₃]₄-R, where R is CH(CH₂OH)CH(COO^?)-OH. 1, is the largest DS fragment thus far isolated containing IdoA2SO₃ as the only uronic acid. Its lower activity (30%) with respect to the parent polymeric DS is explainable by Tollefsen model, requiring longer polyanionic chains for formation of ternary complex with thrombin.     

Pyrrolic Tripodal Receptors for the Molecular Recognition of Carbohydrates: Ditopic Receptors for Dimannosides

Synthetic ditopic receptors, designed for the molecular recognition of dimannosides, have been prepared by bridging two monotopic units effectively recognizing mannosides with linkers of the appropriate size and flexibility, endowed with hydrogen‐bonding groups. Affinities toward the α and β glycosides of the biologically relevant Manα(1–2)Man disaccharide were measured by NMR spectroscopy and isothermal titration calorimetry (ITC) in polar organic media (30–40 % DMF in chloroform). Significant selectivities and affinities in the micromolar range were observed in most cases, with two newly designed receptors being the most effective receptors of the set, together with a distinct preference of the dimannosides for the (S) enantiomer of the receptor in all cases. A 3D view of the recognition mode was elucidated by a combined NMR spectroscopic/molecular modeling approach, showing the dimannoside included in the cleft of the receptor. Compared to the monotopic precursors, the ditopic receptors showed markedly improved recognition properties, proving the efficacy of the modular receptor design for the recognition of disaccharides.     

Arylation with Unsymmetrical Diaryliodonium Salts: A Chemoselectivity Study

Phenols, anilines, and malonates have been arylated under metal‐free conditions with twelve aryl(phenyl)iodonium salts in a systematic chemoselectivity study. A new “anti‐ortho effect” has been identified in the arylation of malonates. Several “dummy groups” have been found that give complete chemoselectivity in the transfer of the phenyl moiety, irrespective of the nucleophile. An aryl exchange in the diaryliodonium salts has been observed under certain arylation conditions. DFT calculations have been performed to investigate the reaction mechanism and to elucidate the origins of the observed selectivities. These results are expected to facilitate the design of chiral diaryliodonium salts and the development of catalytic arylation reactions that are based on these sustainable and metal‐free reagents.     

Surfactant Hydrogels for the Dispersion of Carbon‐Nanotube‐Based Catalysts

Novel hydrogel phases based on positively charged and zwitterionic surfactants, namely, N‐[p‐(n‐dodecyloxybenzyl)]‐N,N,N‐trimethylammonium bromide (pDOTABr) and p‐dodecyloxybenzyldimethylamine oxide (pDOAO), which combine pristine carbon nanotubes (CNTs), were obtained, thus leading to stable dispersions and enhanced cross‐linked networks. The composite hydrogel featuring a well‐defined nanostructured morphology and an overall positively charged surface was shown to efficiently immobilise a polyanionic and redox‐active tetraruthenium‐substituted polyoxometalate (Ru₄POM) by complementary charge interactions. The resulting hybrid gel has been characterised by electron microscopy techniques, whereas the electrostatic‐directed assembly has been monitored by means of fluorescence spectroscopy and ζ‐potential tests. This protocol offers a straightforward supramolecular strategy for the design of novel aqueous‐based electrocatalytic soft materials, thereby improving the processability of CNTs while tuning their interfacial decoration with multiple catalytic domains. Electrochemical evidence confirms that the activity of the catalyst is preserved within the gel media.