Next generation macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation

Bioorganic & Medicinal Chemistry
Emile JubeliWilliam P D Goldring

Abstract

Previously we reported the synthesis and in vitro evaluation of four novel, short-chain cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic hydrophobic regions composed of, or derived from, two 7-carbon chains. Herein we describe a revised synthesis of an expanded library of related cationic lipids to include extended chain analogues, their formulation with plasmid DNA (pDNA) and in vitro delivery into Chinese hamster ovarian (CHO-K1) cells. The formulations were evaluated against each other based on structural differences in the hydrophobic domain and headgroup. Structurally the library is divided into four sets based on lipids derived from two 7- or two 11-carbon hydrophobic chains, C7 and C11 respectively, which possess either a dimethylamine or a trimethylamine derived headgroup. Each set includes four cationic lipids based on an acyclic or macrocyclic, saturated or unsaturated hydrophobic domain. All lipids were co-formulated with the commercial cationic lipid 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC) in a 1:1 molar ratio, along with one of two distinct neutral co-lipids, cholesterol or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in an overall cationic-to-neutral lipid molar ...Continue Reading

References

Jun 16, 2011·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Matthias DittrichGerald Brezesinski
Jul 14, 2012·Langmuir : the ACS Journal of Surfaces and Colloids·Tiago A BalbinoLucimara G de La Torre
Jul 22, 2014·Expert Opinion on Drug Delivery·Andrea PensadoAlejandro Sanchez
Nov 6, 2014·Organic & Biomolecular Chemistry·Zheng HuangXiao-Qi Yu

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