《Molecular Tuning of a Vitamin E-Scaffold pH-Sensitive and Reductive Cleavable Lipid-like Material for Accelerated in Vivo Hepatic siRNA Delivery》 was written by Akita, Hidetaka; Noguchi, Yuki; Hatakeyama, Hiroto; Sato, Yusuke; Tange, Kota; Nakai, Yuta; Harashima, Hideyoshi. Recommanded Product: 2-(Piperidin-4-yl)ethanolThis research focused onvitamin E pH reductive cleavable lipid liver siRNA targeting; drug delivery system; liposomal nanoparticle; liver; siRNA. The article conveys some information:
A lipid nanoparticle (LNP) composed of a series of SS-cleavable and pH-activated lipid-like materials (ssPalm) was previously developed as a platform of a gene delivery system. A tertiary amine and disulfide bonding were employed to destabilize the endosomal membrane and for intracellular collapse. We report herein on the development of a hepatocyte-targeting siRNA carrier by the mol. tuning of the hydrophobic scaffold, and tertiary amine structures. The gene knockdown activity against a hepatocyte-specific marker (factor VII: FVII) was improved when a more fat-soluble vitamin (vitamin E) was employed as a hydrophobic scaffold. Moreover, to allow the tertiary amines to accept protons by sensing a slight change in endosomal acidification, its structural flexibility was minimized by fixing it in a piperidine structure, and the distance between the surface of the particle to the ternary amine was increased. As a result, the pKa value was increased to the approx. 6.18 depending on its distance, while the pKa reached plateau when the tertiary amine was linked by an excess number of linear carbon chains. The pH-dependent membrane destabilization activity, as assessed by a hemolysis assay, was increased in parallel with the pKa value. Moreover, the gene knockdown activity was improved in parallel with hemolytic activity. Finally, further optimization of the lipid/siRNA ratio, and the use of chem. (2′-fluoro) modified siRNA synergistically improved the gene knockdown efficacy to an ED (ED50) of 0.035 mg/kg. The developed ssPalm represents a promising platform for use as a hepatocyte-targeting siRNA carrier. The results came from multiple reactions, including the reaction of 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Recommanded Product: 2-(Piperidin-4-yl)ethanol)
2-(Piperidin-4-yl)ethanol(cas: 622-26-4) have been used as an intermediate in the synthetic preparation of cellular-active allosteric inhibitors of FAKRecommanded Product: 2-(Piperidin-4-yl)ethanol
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem