title: Pyridinium cationic lipids in gene delivery: a structure-activity correlation study.
abstract: Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure-activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results.
authors.affiliation: Department of Marine Sciences, Texas A & M University at Galveston, 5007 Avenue U, Galveston, TX 77551, USA.
authors.forename: Marc Antoniu
authors.initials: MA
authors.lastname: Ilies
authors.forename: William A
authors.initials: WA
authors.lastname: Seitz
authors.forename: Ion
authors.initials: I
authors.lastname: Ghiviriga
authors.forename: Betty H
authors.initials: BH
authors.lastname: Johnson
authors.forename: Aaron
authors.initials: A
authors.lastname: Miller
authors.forename: E Brad
authors.initials: EB
authors.lastname: Thompson
authors.forename: Alexandru T
authors.initials: AT
authors.lastname: Balaban
mesh_terms: D002412:Cations; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D004075:Diglycerides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry; D008081:Liposomes; D015394:Molecular Structure; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D014162:Transfection; D014465:Ultrasonics
chemical_list: C488440:1-(1,3-dimyristoyloxypropane-2-yl)-2,4,6-trimethylpyridinium; D002412:Cations; D004075:Diglycerides; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D011726:Pyridinium Compounds; D004247:DNA; D002784:Cholesterol