Stabilization of Ostwald Ripening in Low Molecular Weight Amino Lipid Nanoparticles for Systemic Delivery of siRNA Therapeutics was written by Gindy, Marian E.;Feuston, Brad;Glass, Angela;Arrington, Leticia;Haas, R. Matthew;Schariter, Joseph;Stirdivant, Steven M.. And the article was included in Molecular Pharmaceutics in 2014.Application of 1224606-06-7 The following contents are mentioned in the article:
Lipid nanoparticles (LNPs) represent the most clin. advanced technol. for the systemic delivery of therapeutic siRNA in vivo. Toward this end, a novel class of LNPs comprising low mol. weight (MW) ionizable amino lipids having asym. architecture was recently reported. LNPs of these amino lipids, termed asym. LNPs, were shown to be highly efficacious and well tolerated in vivo; advances were enabled by improved endosomal escape, coupled with enhanced amino lipid metabolism and clearance. In this work, we show that, in contrast to their desirable pharmacol. performance, asym. LNPs present a significant pharmaceutical developability challenge, namely phys. instability limiting extended shelf life. Using orthogonal characterization methods, we identify the mechanism of LNP instability as Ostwald ripening and establish it to be driven predominantly by the asym. amino lipid component. Through rational optimization of LNP phys. and macromol. properties, we are able to significantly attenuate or entirely eliminate the Ostwald ripening instability. Modulation of LNP size, for example, effectively halts particle growth. Similarly, optimization of LNP macromol. packing through deliberate selection of structurally matched colipids significantly diminishes the rate of ripening. This later exptl. observation is substantiated by mol. dynamics simulations of LNP self-assembly, which establish a quant. dependence of LNP macromol. order on colipid structure. In totality, the exptl. and mol. dynamics outcomes of this work support the rational design of LNP phys. and chem. properties leading to effective Ostwald ripening stabilization and enable the advance of asym. LNPs as a clinic-ready platform for siRNA therapeutics. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Application of 1224606-06-7).
(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Acyl chlorides and acid anhydrides alcoholysis is another way to produce esters. Acyl chlorides and acid anhydrides react with alcohols to produce esters. Anydrous conditions are recommended since both acyl chlorides and acid anhydrides react with water.Application of 1224606-06-7
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Ester – an overview | ScienceDirect Topics