Pyridinium cationic lipids in gene delivery: a structure-activity correlation study.
J Med Chem
; 47(15): 3744-54, 2004 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-15239653
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 11 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.
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Piridínio
/
Portadores de Fármacos
/
Técnicas de Transferência de Genes
/
Diglicerídeos
/
Lipídeos
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos