1887
Volume 2012, Issue 1
  • E-ISSN: 2223-506X

Abstract

Synthetic cationic lipids hold much potential as gene packaging and delivery agents for the treatment of inherited and acquired life threatening diseases, such as cancer, AIDS, cardiovascular diseases, and certain autoimmune disorders. We report the synthesis, self-assembly as characterized by critical micelle concentrations and plasmid DNA gel retardation using two novel cyclic, phosphonate cationic lipids and , which were synthesized by derivatizing two diastereomeric macrocyclic phosphonates and with a 2-carbon hydroxylamine linker, , -dimethylethanolamine (). The production of cyclic phosphonate lipids and in 73% and 60% yields, respectively, was achieved using classical synthetic methods involving nucleophilic substitution at the phosphorus centre. The characterization of these lipids with Mass Spectrometry, 1H, 13C and 31P Nuclear Magnetic Resonance supported the proposed stereochemistry and molecular structure of CHNOP for these lipids. Critical micelle concentrations (CMC) for and were found to be 1.2 mM and 1.4 mM, respectively, at 25°C, providing evidence for the self-assembling ability of these novel cyclic lipids. Finally, lipid-DNA complexes (lipoplexes) formulated at various N/P (+/ − ) molar charge ratios and containing the co-lipid, 1,2-dioleoyl--glycero-3-phosphoethanolamine (DOPE) were shown to retard DNA in an agarose gel retardation assay. The synthesis, aggregation and DNA binding properties of these novel cyclic phosphonate lipids suggest that they may have utility serving as gene packaging and delivery agents.

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2013-06-01
2019-10-19
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