Mixing behaviour of bilayer-forming phosphatidylcholines with single-chain alkyl-branched bolalipids: effect of lateral chain length

Biophys Chem. 2019 Jan;244:1-10. doi: 10.1016/j.bpc.2018.10.003. Epub 2018 Oct 24.


Liposomes are a promising class of drug delivery vehicles. However, no liposomal formulation has been approved for an oral application so far, due to stability issues of the liposomes in the gastrointestinal tract. Herein, we investigate the miscibility of three novel single-chain alkyl-branched bolalipids PC-C32(1,32Cn)-PC (n = 3, 6, 9) with either saturated or unsaturated phosphatidylcholines by means of differential scanning calorimetry (DSC), transmission electron microscopy (TEM) of stained samples, vitrified specimens, or replica of freeze-fractured samples, and dynamic light scattering (DLS). The novel bolalipids contain lateral alkyl chains of different length in 1- and 32-position of the long membrane-spanning C32 alkyl chain. We will show for the first time that these single-chain alkyl-branched bolalipids show a miscibility with bilayer-forming phospholipids-by maintaining the vesicular aggregate structure-due to the lateral alkyl substituents located next to the phosphocholine headgroup of the bolalipid. We are convinced that these alkyl side chains are able to fill the void volume, which is created when unmodified single-chain bolalipids are inserted in a transmembrane fashion into a phospholipid bilayer. Consequently, the miscibility of our alkyl-chained bolalipids with bilayer-forming phospholipids rose with increasing lengths of the lateral alkyl chain of the bolalipid. Finally, we were successful in preparing liposomes from various bolalipid/phospholipid mixtures, which were stable in size upon storage for at least 21 days. These mixed liposomes (bolasomes) could be used as oral drug delivery systems in the near future.

Keywords: Bolaamphiphiles; Bolalipids; Bolasomes; Liposomes; Mixing behaviour; Phospholipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Drug Delivery Systems
  • Lipid Bilayers / chemistry*
  • Liposomes / chemistry*
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Phosphatidylcholines / chemistry*


  • Lipid Bilayers
  • Liposomes
  • Phosphatidylcholines