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The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range

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Abstract

In this paper we investigate the pseudo-ternary phase diagram of glycerol monooleate (GMO), a cationic lipid (DOTAP – 1,2-dioleoyl-3-trimethylammonium propane), and a “PEGylated” lipid (DOPE-PEG – 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 kDa]) in excess water. We use small angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (Cryo-EM) to map out a phase diagram in a regime of low DOPE-PEG content (1–5 mol%), which is pertinent for the application of lipid systems as carriers of biomolecular cargo to cells. Pure GMO is known to self-assemble into bicontinuous cubic phases of the gyroid type at low water content and of the diamond type in excess water. These complex structures have numerous advantages reaching beyond drug delivery, e.g. as protein crystallization matrices, but their formulation is challenging as very small contents of guest molecules can shift the phase behavior towards other geometries such as the lamellar phase. In this work, we show that the ternary GMO/DOTAP/DOPE-PEG system allows the stabilization of bicontinuous cubic phases in excess water over a wide composition range. The symmetry of the phase can be tuned by varying the amount of PEGylated lipid, with the primitive type dominating at low DOPE-PEG content (1–3 mol%) and the diamond phase arising at 5 mol% DOPE-PEG. In addition, we found that the diamond phase is virtually non-responsive to electrostatic swelling. In contrast, primitive bicontinuous cubic lattice dimensions swell up in equilibrium to 650 Å with increased cationic lipid content.

Graphical abstract: The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range

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Publication details

The article was received on 09 Oct 2018, accepted on 14 Nov 2018 and first published on 14 Nov 2018


Article type: Paper
DOI: 10.1039/C8SM02059K
Citation: Soft Matter, 2019, Advance Article
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    The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range

    S. S. W. Leung and C. Leal, Soft Matter, 2019, Advance Article , DOI: 10.1039/C8SM02059K

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