Archaea are single-celled organisms that differ from bacteria and eukaryotes such as animals, plants, and fungi. For example, their cell membranes contain phospholipids with branched hydrocarbon chains substituted with methyl groups (pictured schematically), as opposed to the linear fatty acid chains found in phospholipids in bacteria and eukaryotes. Archaeal membranes are very stable and have a low permeability for, e.g., protons. Liposomes are artificial spheres made from lipid bilayers, similar to cell membranes. They can be used, e.g., for drug delivery, but sometimes suffer from uncontrolled leakage of their cargo.

Inspired by the cell membranes of archaea, Daniel S. Kohane, Harvard Medical School, Boston, MA, USA, and colleagues have incorporated methyl-branched phospholipids into the lipid bilayers of liposomes to improve their properties for drug delivery. The team used diphytanoylphosphatidylcholine (4ME-PC), an ester phospholipid with four methyl groups in the hydrocarbon chain, to prepare liposomes, together with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphatidylglycerol (DSPG), and cholesterol.

The researchers used the liposomes for the encapsulation and release of different water-soluble molecules, including the fluorophore sulforhodamine B and the anesthetic tetrodotoxin (TTX). They found that compared with similar liposomes without methyl groups, the methyl-branched liposomes increased the loading and slowed down the release of encapsulated compounds. The team also evaluated the drug release properties in vivo, using rats to test the duration of local anesthesia using encapsulated TTX. They found that conventional liposomes worked for 16 h, while the methyl-branched liposomes prolonged the effect to 70 h. These results are promising for the development of liposome-based depot systems for drug delivery.

• Methyl-Branched Liposomes as a Depot for Sustained Drug Delivery,
  Yang Li, Rachelle Shao, Claire A. Ostertag-Hill, Matthew Torre, Ran Yan, Daniel S. Kohane,
  Nano Lett. 2023.
  https://doi.org/10.1021/acs.nanolett.3c02137

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