Detection and identification of designer drugs by nanoparticle-based NMR chemosensing.

Properly designed monolayer-protected nanoparticles (2 nm core diameter) can be used as nanoreceptors for selective detection and identification of phenethylamine derivatives (designer drugs) in water. The molecular recognition mechanism is driven by the combination of electrostatic and hydrophobic interactions within the coating monolayer. Each nanoparticle can bind up to 30-40 analyte molecules. The affinity constants range from 105 to 106 M-1 and are modulated by the hydrophobicity of the aromatic moiety in the substrate. Detection of drug candidates (such as amphetamines and methamphetamines) is performed by using magnetization (NOE) or saturation (STD) transfer NMR experiments. In this way, the NMR spectrum of the drug is isolated from that of the mixture, allowing broad-class multianalyte detection and even identification of unknowns. The introduction of a dimethylsilane moiety in the coating monolayer allows performing STD experiments in complex mixtures. In this way, a detection limit of 30 µM is reached with standard instruments.

Nanoparticle-Assisted Affinity NMR Spectroscopy: High Sensitivity Detection and Identification of Organic Molecules.

A simple and effective method for high-sensitivity NMR detection of selected compounds is reported. The method combines 1D NMR diffusion filter experiments and small monolayer-protected nanoparticles as high-affinity receptors. Once bound to the nanoparticles, the diffusion coefficient of the analyte decreases in such way that spectral editing based on diffusion filters can separate its signals from those of other mixture components. Using nanoparticles functionalized with Zn2+ -triazacyclonane complexes, detection and identification of phosphorylated organic molecules can be achieved. Diphenyl phosphate can be detected at 25 micromolar concentration with good selectivity. The selectivity toward organic carboxylates is enhanced at pD=3.75. In these conditions, commercial tablets containing betamethasone phosphate and a large excess of benzoate could be successfully analyzed.

Nanoparticle-assisted NMR detection of organic anions: from chemosensing to chromatography.

Monolayer-protected nanoparticles provide a straightforward access to self-organized receptors that selectively bind different substrates in water. Molecules featuring different kinds of noncovalent interactions (namely, hydrophobic, ion pairing, and metal-ligand coordination) can be grafted on the nanoparticle surface to provide tailored binding sites for virtually any class of substrate. Not only the selectivity but also the strength of these interactions can be modulated. Such recognition ability can be exploited with new sensing protocols, based on NMR magnetization transfer and diffusion-ordered spectroscopy (DOSY), to detect and identify organic molecules in complex mixtures.

"NMR chemosensing" using monolayer-protected nanoparticles as receptors.

A new sensing protocol based on NMR magnetization transfer sequences and the molecular recognition abilities of nanoparticles allows the detection and identification of organic molecules in complex mixtures.

Left-sided gallbladder (sinistroposition) with duplication of the common bile duct.

A left-sided gallbladder sinistroposition is a rare finding. These gallbladders are situated left of the falciform ligament and are located under the left lobe of the liver, between segments III and IV. Common bile duct duplication is also rare, and its cause is not yet fully understood. A 55-year-old woman presented to our hospital with symptoms of chronic cholecystitis. During the laparoscopic cholecystectomy, it was discovered that not only was her gallbladder to the left of the falciform ligament, but she also had a duplication of her common bile duct. Although cases of left-sided gallbladders have been reported in the past, and there has been a report of a sinistroposition of both gallbladder and common bile duct, we believe this is the first reported case of left-sided gallbladder sinistroposition with the complete duplication of the common bile duct. As we learn more about various anatomical anomalies of the gallbladder through the use of laparoscopic cholecystectomies, surgeons encountering a left-sided gallbladder should be aware of the potential for associated anomalies.

Polymeric sustained local drug delivery system for the prevention of vascular intimal hyperplasia.

Anastomotic intimal hyperplasia (IH) is a major cause of both autologous vein and synthetic vascular graft failure. We have previously published data suggesting that cyclosporin may reduce the development of IH in a canine model. However, systemic administration of cyclosporin could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of cyclosporin from a polymeric vascular wrap will prevent the development of IH. To test this hypothesis, we developed a controlled release vascular wrap (sheet/ring) using a poly(ethylene glycol) (PEG) hydrogel. Sterilization of the polymers was performed using the ethylene oxide and hydrogen peroxide sterilization methods. It was found that except for one combination (8000 molecular weight and 1:1 crosslinking ratio), the differences in the swelling ratios for the sterilized and unsterilized hydrogels were not statistically significant. Release studies from unsterilized and ethylene oxide-sterilized PEG hydrogels were conducted. It was found that release lasted for approximately 50 h for sterilized as well as unsterilized PEG hydrogels. Acute animal studies, to test the deployment of both the polymeric sheets and rings to the adventitial surface of native arteries and veins, were completed successfully.