Article ID Journal Published Year Pages File Type
1251756 Chemistry and Physics of Lipids 2014 20 Pages PDF
Abstract

•Synthesis of amphiphilic cationic glycol lipids.•Introducing rigid polyene chains next to flexible saturated chains.•Self-assembly to aggregates, liposomes and lipoplexes not controllable.•Transfection to CHO-K1 cells not following a structure–activity relationship.

Cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic C20:5 and C30:9 chains next to saturated flexible alkyl chains of variable lengths C6-20:0. Surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/DNA complexes (lipoplexes) were established using three formulations (no co-lipid, DOPE as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected using small angle X-ray diffraction to explore details of the partially ordered structures of the systems that constitute the series. Transfection and cytotoxicity of the lipoplexes were evaluated by DNA delivery to Chinese hamster ovary (CHO-K1) cells using the cationic glycerol phospholipid 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) as a reference compound.The uncontrollable self-association of the molecules in water resulted in aggregates and liposomes of quite different sizes without a structure–property relationship. Likewise, adding DNA to the liposomes gave rise to unpredictable sized lipoplexes, which, again, transfected without a structure–activity relationship. Nevertheless, one compound among the novel lipids (C30:9 chain paired with a C20:0 chain) exhibited comparable transfection efficiency and toxicity to the control cationic lipid EPC. Thus, the presence of a rigid polyene chain in this best performing achiral glycol lipid did not have an influence on transfection compared with the chiral glycerolipid reference ethyl phosphocholine EPC with two flexible saturated C14 chains.

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Physical Sciences and Engineering Chemistry Chemistry (General)
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