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Membrane-forming properties of cationic lipids bearing oxyethylene-based linkages

Bhattacharya, Santanu and Dileep, Padinjarae Vangasseri (2003) Membrane-forming properties of cationic lipids bearing oxyethylene-based linkages. In: Journal of Physical Chemistry B, 107 (16). pp. 3719-3725.

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The membrane-forming properties of four cationic lipids (1-4) having varying number of oxyethylene (-CH2-CH2-O-)(n) units at the linkage region between the pseudo-glyceryl backbone and the hydrocarbon chains have been described. Lipids 1 and 2 have an equal number of oxyethylene units attached to both C-I and C-2 positions of the pseudo glyceryl backbone, while the other two, 3 and 4, are unsymmetrical in terms of the number of oxyethylene linkages. The membrane characteristics of these lipids were compared with a control lipid, 5, bearing just an ether functionality at both the C-I and C-2 positions. All the lipids (1-5) formed stable suspensions in water which showed the presence of membranous aggregates as revealed by electron microscopy (TEM). The lipids 1, 2, and 4 showed distinct spherical aggregates in TEM, whereas 3 exhibited particles of irregular morphologies. The lipid suspensions were further characterized by dynamic light scattering and zeta potential measurements. Except for lipid 3, zeta potentials of such lipid aggregates were found to be substantially lower than their diether analogue, 5. X-ray diffraction studies with the lipid cast films revealed that incorporation of oxyethylene units at the linkages increased the unit bilayer thickness of the membranous assemblies. Temperature-dependent fluorescence anisotropy experiments using the lipid-soluble probe 1,6-diphenylhexatriene (DPH) suggested a disordered environment in these lipid aggregates even in their gel states. The aggregates formed by lipid 3 showed the lowest DPH anisotropy values. Clear thermotropic phase transitions typical of membranous assemblies were observed for all the lipid suspensions by differential scanning calorimetry. The phase transitions were reversible and exhibited large hysteresis indicating that the observed phase transitions were of first order.

Item Type: Journal Article
Publication: Journal of Physical Chemistry B
Publisher: American Chemical Society
Additional Information: Copyright of this article belongs to American Chemical Society.
Keywords: Gene transfection efficiency;pseudoglyceryl backbone;cholesteryl skeleton;complexes;delivery;features;serum;dna;liposomes;mechanism.
Department/Centre: Division of Chemical Sciences > Organic Chemistry
Date Deposited: 24 Nov 2009 07:03
Last Modified: 19 Sep 2010 04:55
URI: http://eprints.iisc.ac.in/id/eprint/17118

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