- The use of nanoparticles to deliver nitric oxide to hepatic stellate cells for treating liver fibrosis and portal hypertension
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Polymeric nanoparticles are designed to transport and deliver nitric oxide (NO) into hepatic stellate cells (HSCs) for the potential treatment of both liver fibrosis and portal hypertension. The nanoparticles, incorporating NO donor molecules (S-nitrosoglutathione compound), are designed for liver delivery, minimizing systemic delivery of NO. The nanoparticles are decorated with vitamin A to specifically target HSCs. We demonstrate, using in vitro and in vivo experiments, that the targeted nanoparticles are taken up specifically by rat primary HSCs and the human HSC cell line accumulating in the liver. When nanoparticles, coated with vitamin A, release NO in liver cells, we find inhibition of collagen I and α-smooth muscle actin (α-SMA), fibrogenic genes associated with activated HSCs expression in primary rat liver and human activated HSCs without any obvious cytotoxic effects. Finally, NO-releasing nanoparticles targeted with vitamin A not only attenuate endothelin-1 (ET-1) which elicites HSC contraction but also acutely alleviates haemodynamic disorders in bile duct-ligated-induced portal hypertension evidenced by decreasing portal pressure (≈20%) and unchanging mean arterial pressure. This study clearly shows, for the first time, the potential for HSC targeted nanoparticle delivery of NO as a treatment for liver diseases with proven efficacy for alleviating both liver fibrosis and portal hypertension. Nanoparticles with a typical size of 35 nm are presented for the delivery of nitric oxide to hepatic stellate cells for the potential treatment of liver fibrosis and portal hypertension. The introduction of vitamin A on the nanoparticles surface allows to specifically target hepatic stellate cells. In vivo experiments, using rat models, demonstrate the accumulation of nanoparticles in liver.
- Duong, Hien T. T.,Dong, Zhixia,Su, Lin,Boyer, Cyrille,George, Jacob,Davis, Thomas P.,Wang, Jianhua
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- Intracellular nitric oxide delivery from stable NO-polymeric nanoparticle carriers
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The encapsulation of S-nitrosoglutathione into polymeric nanoparticles substantially improves NO stability in aqueous media without affecting the efficacy of intracellular delivery. The combination of nano-NO delivery and chemotherapy has been found to enhance antitumour activity of chemotherapeutics, as demonstrated using preliminary in vitro experiments with neuroblastoma cells.
- Duong, Hien T. T.,Kamarudin, Zulkamal M.,Erlich, Rafael B.,Li, Yang,Jones, Mathew W.,Kavallaris, Maria,Boyer, Cyrille,Davis, Thomas P.
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supporting information
p. 4190 - 4192
(2013/05/23)
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- REACTIVE LIQUID MODIFIERS
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Epoxy reactive liquid modifiers include acrylate functionalized compounds, acrylamide functionalized compounds, oxalic amide functionalized compounds, actoacetoxy functionalized urethanes and acetoacetoxy functionalized polyalkenes. The reactive liquid modifiers are incorporated into epoxy resin compositions comprising a curable epoxy resin, an amine curing agent, and the reactive liquid modifier, wherein the reactive liquid modifier is polymerized to form at least one of an interpenetrating polymer network and a semi-interpenetrating polymer network with the curable epoxy resin.
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Page/Page column 35
(2010/04/03)
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- Azlactone-based surfactants
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A compound of the formula STR1 wherein Q is an organic group of at least two carbon atoms having at least m substituents, m is 1, 2, 3, 4, 5 or 6, and n is 0 or 1. R3 is H or methyl, R8 and R9 are independently hydrogen, alkyl group or aryl, R12 and R13 are independently selected from the group consisting of an alkyl group or a cation, and R10 is independently selected from the group consisting of hydrogen, an alkyl group, aryl group, and highly-fluorinated alkyl group, R4 may be hydrogen or alkyl group, and R7 may be hydrogen or lower alkyl group, provides excellent stability to dispersions.
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- Process for the acrylamidoacylation of alcohols
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The present invention provides a dramatically improved process for the preparation of acrylamide and methacrylamide functional monomers, oligomers, and polymers that avoids the use of acidic catalysts which can cause undesired side reactions. The present invention process involves reacting an alkenyl azlactone with a hydroxy functional compound in the presence of a catalytic amount of either a bicyclic amidine or a trivalent phosphorus compound. These efficient basic catalysts provide unexpectedly increased reaction rates under mild conditions.
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