Mixing behaviour of asymmetrical glycerol diether bolalipids with saturated and unsaturated phosphatidylcholines.

Liposomes have received attention as a promising class of drug delivery vehicles. To date, many approaches have been tried developing liposomes for oral use. However, no liposomal formulation is on the market so far that is approved for oral application. In this study, we investigate the miscibility of two glycerol diether bolalipids with classical saturated and unsaturated phosphatidylcholines by means of differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Our bolalipids contain a long C32 alkyl chain bound to glycerol in the sn-3 position and a short C16 in the sn-2 position, which further carries a racemic methyl branch. The sn-1 position of the glycerol as well as the end of the long C32 alkyl chain contain polar headgroups: either two phosphocholine headgroups (PC-Gly(2C16Me)C32-PC) or a phosphocholine and a phosphodimethylethanolamine headgroup (PC-Gly(2C16Me)C32-Me2 PE). We demonstrate that glycerol diether bolalipids show better miscibility with unsaturated phosphatidylcholines than with saturated ones. Both bolalipids in mixture with the unsaturated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) form liposomes, which are stable in size upon storage. These mixed bolalipid/phospholipid vesicles could be used as an oral liposomal formulation in the future.