Liposomes and Membranes
Liposomes are artificial vesicles, ranging in size from approximately 25 nm to 2.5 μm, which may be composed of a variety of synthetic or naturally derived phospholipids.
They are used in the pharmaceutical industry, and more than 15 liposome-based drugs currently have clinical approval for a range of medical applications, including infection control, vaccine delivery or anticancer medications. Many more are in current clinical trials. They are beneficial for drug delivery because they can give better therapeutic efficacy and safety over existing formulations.
This is based on several important advantages, including improved solubility of certain molecules (that might otherwise not be soluble in the blood), protection of an entrapped drug from degradation, increased cellular uptake and improvements in a drug’s pharmacokinetic and tissue distribution profile.
We have been using liposomes and membranes to deliver Wnt proteins to try and improve bone fracture repair.
Wnt proteins are some of the most ancient known signalling proteins. They're found throughout the animal kingdom - from sponges to man - and play fundamental roles in animal development and disease. The molecular pathways that Wnt proteins activate also regulate stem cell division, and can sometimes promote tissue regeneration in animals such as amphibians.
We found that we could increase the frequency of cells by chemically modulating Wnt signalling. We published this paper in Stem Cells in 2015, and you can find it here, and also an TV interview we did about it here.
We next found, like others, that Wnt proteins can be stabilised in special type of PEGylated liposome, which are stable for long periods of time in the body. This is published, and you can read it here.
More recently, we have found that Wnt proteins, which are lipid modified – this is the reason why we think they interact with membranes – interact directly with living cell membranes, which offers clues to how Wnt proteins move around in the human body. You can read about it here and watch a video of Wnt proteins moving around on cell membranes below:
We’re now investigating whether we can directly use these sorts of technologies, in addition to polymersomes to speed up bone repair.
Wnt stimulates bone cell activity (in purple)
Diagram of a Wnt-associated liposome, phospholipids in blue, PEG molecules in orange, Wnt protein in red
Transmission electron microscope image of liposomes