CPL CHEMISTRY AND Chemistry and Physics of Lipids PHYSICS OF LIPIDS ELSEVIER 82 (1996) 89 100 Synthesis and aggregation properties of dialkyl polyoxyethylene glycerol ethers M. Jayne Lawrence*, Simon M. Lawrence ~, Sushil Chauhan 2, David J. Barlow Department of Pharmacy, King's' College London, Unirersi O' O/Lomton, Mam'esa Road London SW3 6LX, ('K Received 28 December 1995: revised 22 April 1996: accepted 3 May 1996 Abstract Two series of symmetric 1,2-dialkyl-rac-glycerol ether surfactants containing a polydisperse non-ionic monomethyl polyoxyethylene glycol (MPEG) head group have been prepared using one of two similar four stage reaction pathways. Both schemes start with isopropylidene-rac-glycerol. In the first scheme the unifunctional MPEG was brominated and added to isopropylidene-rac-glycerol directly. In the second pathway the underivatized MPEG was attached to isopropylidene-rac-glycerol via a tosyl glycerol derivative. In both reaction schemes the alkyl chains were introduced onto the monomethyl polyoxyethylene glycerol using a Williamson ether type reaction. A third, six stage, synthetic route allowed the production of asymmetric 1,2-dialkyl-rac-glycerol ether surfactants. In this scheme the first alkyl chain was added to isopropylidene-rac-glycerol directly, while the second chain was added after selective (trityl group) protection of the primary hydroxyl of the monoalkyl glycerol ether. In this route the polyoxyethylene glycol (PEG) chain was added terminally. In all schemes the crude surfactants were purified either by column chromotography or by a simple but effective washing and molecular distillation procedure. The aggregation behaviour of the novel surfactants in aqueous solution is reported, and general trends noted as to the influences of the hydrophobe and head group lengths on the nature of the aggregates formed. Keywordv: Synthesis; Novel non-ionic surfactants: Dialkyl polyoxyethylene glycerol ethers; Aggregation properties 1. Introduction For many years phospholipid vesicles (lipo- * Corresponding author. Tel.: +44 171 3334808: fax: +44 somes) have been under investigation as carrier 171 3515307; e-mail: jayne.lawrence@kcl.ac.uk systems for drugs [1]. However, in vitro liposomes ~Present address: Chauvin Pharmaceuticals, Harold Hill, generally revert back to the multilamellar liquid Romford, Essex. 2 Present address: SmithKline Beecham, Mundells, Welwyn crystalline phases from which they originate [2], Garden City, Herts. while in vivo they are rapidly removed from the 0009-3084/96/$15.00 ~", 1996 Elsevier Science Ireland Ltd. All rights reserved Pll S0009- 3084(96)02566- 2