Journal of Colloid and Interface Science 315 (2007) 701–713 www.elsevier.com/locate/jcis Aqueous self-assembly of phytantriol in ternary systems: Effect of monoolein, distearoylphosphatidylglycerol and three water-miscible solvents Pia Wadsten-Hindrichsen, Johanna Bender, Johan Unga, Sven Engström ∗ Pharmaceutical Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden Received 15 May 2007; accepted 5 July 2007 Available online 10 July 2007 Abstract The aqueous phase behavior of phytantriol (PT) in mixtures of monoolein (MO), distearoylphosphatidylglycerol (DSPG), propylene glycol (PG), polyethylene glycol 400 (PEG 400) and 2-methyl-2,4-pentanediol (MPD) was investigated by visual inspection, polarized light microscopy and small angle X-ray diffraction at room temperature. The phase diagrams of PT and MO in water are qualitatively very similar and PT/MO mixtures in excess water form one cubic phase of space group Pn3m irrespective of mixing ratio. The addition of the charged membrane lipid DSPG to the PT system gives rise to a considerable water swelling of the cubic phases as well as the occurrence of a cubic phase of space group Im3m. Whereas all three solvents studied give rise to a sponge (L 3 ) phase in the MO–water system, this phase was only found when MPD was added to the PT–water system. The results are discussed with respect to the chemical differences between PT and MO.  2007 Elsevier Inc. All rights reserved. Keywords: Cubic phase; Sponge phase; Lamellar phase; Phase behavior; Small angle X-ray diffraction; Phytantriol; Monoolein 1. Introduction The polar lipid monoolein (MO), see Fig. 1, has received a considerable interest due to its fascinating phase behavior in water. In contrast to membrane lipids, which form lamellar or reversed hexagonal liquid crystalline phase in aqueous solution, MO forms a bicontinuous cubic liquid crystalline phase in ex- cess of water, for a review see [1]. This cubic phase, of space group Pn3m, consists of one congruent MO bilayer surrounded by two water channel systems, and is often modeled as an infi- nite periodic minimal surface (IPMS) of the diamond (D) type. There also exists a cubic phase at lower water content which is of the Ia3d type and modeled as a gyroid (G) surface [2]. The cubic phase of MO can incorporate hydrophilic, lipo- philic and amphiphilic substances of various size into its structure and has therefore been utilized for drug delivery [3–5], biosensors [6,7], drug partition studies [8], oligonu- cleotide electrophoresis [9] and membrane protein crystalliza- * Corresponding author. Fax: +46 31 160 062. E-mail address: sven.engstrom@chalmers.se (S. Engström). tion [10,11]. The addition of a third substance to a MO–water system may transform the cubic phase into liquids such as mi- cellar and sponge phases [12,13], or liquid crystals such as lamellar, hexagonal, reversed hexagonal and other cubic phases, e.g., [14–16]. The peculiar aqueous phase behavior of MO is also found for certain polar lipids based on the phytanyl chain [17,18]. In a recent publication, the similarities in aqueous phase be- havior of phytantriol (PT), see Fig. 1, and MO was demon- strated by Barauskas and Landh [17]. The binary MO–water and PT–water phase diagrams are given in Figs. 2a and 2b, re- spectively. The most obvious differences between MO and PT are their swelling ability and the stability of the various phases with temperature. The lower swelling of PT and its tendency to form the reversed hexagonal and reversed micellar phases at lower temperatures reflects its more hydrophobic charac- ter. Compared to MO, the number of studies on PT presented in the scientific literature is much smaller. Hartley et al. used a cubic phase of PT in water in order to bind the toxin ricin by incorporating certain galactose amphiphiles [19]. PT has also 0021-9797/$ – see front matter  2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jcis.2007.07.011