Fluorinated vesicles.

Abstract

Stable fluorinated vesicles--i.e. vesicles with a hydrophobic and lipophobic fluorinated film within their bilayer membranes--have been obtained from a variety of neutral, zwitterionic or anionic fluorinated amphiphiles, including single chain phosphocholine derivatives, double-chain phospholipids, glycolipids and glycophospholipids, as well as from combinations of standard phospholipids with amphiphilic mixed fluorocarbon/hydrocarbon compounds. The strong hydrophobic interactions developed by perfluoroalkyl chains result in increased membrane stability, as strikingly illustrated by the fact that even short single-chain fluorinated amphiphiles can form stable, heat-sterilizable vesicles without the need for any additive. They also result in increased versatility in the aggregation behavior of fluorinated surfactants, as shown by the formation, depending on molecular structure and experimental conditions, of a range of supramolecular assemblies other than vesicles, including disks, helical tubules and fibers, for example from fluorinated glycolipids. The more impermeable, adjustable fluorinated core within the liposomal membrane confers to liposomes added drug and probe encapsulation stability as compared to their hydrogenated analogs, whether in buffer or in serum. Fluorinated vesicles made from perfluoroalkylated phospholipids were also found to have 3 to 6 times longer circulation half-lives in mice than similarly sized conventional DSPC/cholesterol liposomes. Finally, the incorporation of mixed fluorocarbon/hydrocarbon alkanes or alkenes into standard liposomes may provide an alternative, straightforward and cost efficient approach to fluorinated vesicles.