Dear Tony Tiller ,

First of all a little correction. Soap makes micelles, liposomes can be a confusing name but normally it is used for structures that form so-called bilayers.

Structures like micelles require molecules that are amphiphilic. Meaning one part is hydrophobic and one part is hydrophilic. Fat (or better triglycerides) are solely hydrophobic. By ‘cutting off’ the fatty acyl chains you get free fatty acids with a long (hydrophobic) fatty acyl chain and a (hydrophilic) headgroup. Now they have the characteristics of a soap (or emulsifier like) molecule.

See for a bit more details for example:

https://www.elcamino.edu/faculty/pdoucette/7B-Saponification.pdf

http://web.fscj.edu/Milczanowski/eleven/Soap.pdf

Hope this clarifies what’s happening during saponification and why it works to make micelles.

Rob Keller Thanks for your response. So the "cutting off" id the hydrolysis of ester bonds between the phosphate heads and acylchains? Are you saying saponification cannot not be done with liposomes? Is saponification part of the pH gradient changes in active loading liposome preparation?

Dear Tony,

I feel you talk about different things.

Saponification means basically forming soap like molecules. While forming liposomes (and encapsulated/loading something) is a completely other matter which has in my view nothing to do with saponification.

The breaking I tried to explain is the ‘splitting’ of the ester bond that binds fatty acids to glycerol (forming triglycerides). The saponification is basically the reverse process (see the links I included in my previous answer).

Whether pH gradients help when you want to include soap like molecules (if that is what you mean) depends very much on what type of fats you use and what kind of counter ions (sodium-, potassium, calcium- and so on) are present.

Hope this clarifies it all a bit more.

Rob Keller Thank you this does clarify a few things. The reason I mention liposomes is because of a patent I read which confused me:

An esterification/saponification-based method for liposomal loading

https://patents.google.com/patent/WO2017120190A1/en

I was wondering how the saponification method relates to this but I think it is the encapsulated compound itself which is being esterified/saponified.

There is also a company claiming to use "saponification method" to make their liposomes which made me question the validity of their claim.

Yes this clarifies a lot ;-)

Indeed this patent describes the use of an ester type compound (intrinsically hydrophobic) that is once loaded into liposomes is saponified into a hydrophilic one.