Exploration of catalysis activation emergency as a function of gold nanoparticle surface morphology

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2008.Includes bibliographical references (p. 45).The application of rippled gold nanoparticles with bi-ligand surface morphology as a catalyst was tested. The hydrolysis of 2,4-dinitrophenyl acetate (DNPA) served as the catalytic reaction being analyzed and the bi-ligand composition used was 16-mercaptohexadecanoic acid to imidazole thiol (MHA to IT). The influence of temperature on catalytic reaction of DNPA with the MHA: IT system was tested for ligand rations of 2:1, 1:2, and 1:1 by monitoring the catalytic system on a UV-VIS spectrometer. Catalytic rate constants were obtained and found to increase with increased temperature. The measured catalytic rate constants were greatest overall for the 1:1 system, followed by the 1:2 system, and lastly the 2:1 system. The activation energy for each ligand-ratio system was measured and found to be 22.17 kJ/mol for the 2:1 system, 14.7 kJ/mol for the 1:2 system, and 26.52 for the 1:1 system. The 2:1 and 1:2 systems followed the trend of lower activation energy values for systems with faster rates; however the 1:1 system did not fit this trend as it resulted in the highest activation energy value as well as the fastest reaction rates.by Cristina F. Stefanescu.S.B

Elasticity and safety of alkoxyethyl cyanoacrylate tissue adhesives

Cyanoacrylate glues are easily applied to wounds with good cosmetic results. However, they tend to be brittle and can induce local tissue toxicity. A series of cyanoacrylate monomers with a flexible ether linkage and varying side-chain lengths was synthesized and characterized for potential use as tissue adhesives. The effect of side-chain length on synthesis yield, physical and mechanical properties, formaldehyde generation, cytotoxicity in vitro and biocompatibility in vivo were examined. The incorporation of etheric oxygen allowed the production of flexible monomers with good adhesive strength. Monomers with longer side-chains were found to have less toxicity both in vitro and in vivo. Polymerized hexoxyethyl cyanoacrylate was more elastic than its commercially available and widely used alkyl analog 2-octyl cyanoacrylate, without compromising biocompatibility.DuPont MIT Allianc

Magnetically Triggered Nanocomposite Membranes: A Versatile Platform for Triggered Drug Release

Author Manuscript 2012 March 9.Drug delivery devices based on nanocomposite membranes containing thermoresponsive nanogels and superparamagnetic nanoparticles have been demonstrated to provide reversible, on−off drug release upon application (and removal) of an oscillating magnetic field. We show that the dose of drug delivered across the membrane can be tuned by engineering the phase transition temperature of the nanogel, the loading density of nanogels in the membrane, and the membrane thickness, allowing for on-state delivery of model drugs over at least 2 orders of magnitude (0.1−10 μg/h). The zero-order kinetics of drug release across the membranes permit drug doses from a specific device to be tuned according to the duration of the magnetic field. Drugs over a broad range of molecular weights (500−40000 Da) can be delivered by the same membrane device. Membrane-to-membrane and cycle-to-cycle reproducibility is demonstrated, suggesting the general utility of these membranes for drug delivery.Ruth L. Kirschstein National Research Service AwardNational Institutes of Health (U.S.) (Award F32GM096546

Near-infrared-actuated devices for remotely controlled drug delivery

A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.National Institutes of Health (U.S.) (Grant GM073626)Massachusetts Institute of Technology. Laser Biomedical Research Center (Sanofi Aventis (Firm) Biomedical Innovation Funding Award)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service AwardNational Institutes of Health (U.S.) (Grant F32GM096546

Clinical Impact and Safety of Anticoagulants for Portal Vein Thrombosis in Cirrhosis

Objectives: Portal vein thrombosis (PVT) is a frequent complication of cirrhosis. Benefit, safety, and duration of anticoagulant treatment in this setting are controversial issues. The aim of this study was to analyze the course of PVT in a large cohort of cirrhotic patients undergoing or not anticoagulation therapy. Methods: The data of 182 patients who presented between January 2008 and March 2016 with cirrhosis and PVT with at least 3 months of follow-up after the first PVT detection were analyzed. Eighty-one patients received anticoagulants and 101 were untreated per physician discretion. Results: The extension of the thrombosis decreased by >50% in 46 (56.8%, with complete recanalization in 31/46) patients under anticoagulation and in 26 (25.7%) untreated patients. Of the 46 patients who underwent recanalization, 17 (36%) suffered recurrent thrombosis after stopping anticoagulation therapy. Kaplan\u2013Meier analysis showed a higher survival rate in the treated group (p = 0.010). At multivariate analysis, anticoagulation was an independent factor associated with longer survival (HR:0.30, CI:0.10\u20130.91, p = 0.014). The Child\u2013Turcotte\u2013Pugh classes B/C negatively influenced survival (hazard ratio, (HR):3.09, confidence interval (CI):1.14\u20138.36, p = 0.027 for Child\u2013Turcotte\u2013Pugh B and HR:9.27, CI:2.67\u201332.23, p < 0.001 for Child\u2013Turcotte\u2013Pugh C). Bleeding complications occurred in 22 (21.8%) untreated and 16 (19.7%) treated patients, but in only four cases was it judged to be related to the anticoagulant treatment. No death was reported as a consequence of the bleeding events. Conclusions: Anticoagulant treatment is a safe and effective treatment leading to partial or complete recanalization of the portal venous system in 56.8% of cases, improving the survival of patients with cirrhosis and PVT. Discontinuation of the therapy is associated with a high rate of PVT recurrence