Here’s the results of my PITA (Pain In The ---) Project!! Remember Don’t crucify me I’m Just the messenger! If and when this publication reaches public availability I’ll link or name it but for the price I’m seeing, probably won’t be on everyone’s must have list. Like “Practicing medicine without a License!”
One of the most challenging aspects in liposome application is the loading of the vesicles and has been the bases of most of the research. The one that has the most success has been ultrasound. Which is basically sound waves far exceeding the normal hearing range of human ears, in water. The strength of the waves and the frequencies of the waves have a lot of effects on their abilities to perform different tasks.
In liposome applications it is common knowledge that preparation and formation of the liposome prior to being sonically processed is one of the key’s to successful encapsulation. This process of producing liposome’s involves the use of solvents, wetting and dehydrating the molecules so it can be assembled and forming of the inner and outer core.
In this presentation this process has already been completed and what is known as a ECL (empty core liposome) These vesicles are then placed in a media and the process of loading through ultrasound is what is explained.
Control of the amount of frequency, power and time factor has such varied opinion’s and research result’s that it can be mind spinning. What the latest findings are that, although excess power and time can completely destroy the liposome altering these factors can have other results. Here’s some examples of the type of damage that can be done by improper ultrasound application.
The general understanding up to this has been that the drug or whatever is driven thru the bilayer into the inner part of the liposome. This is the theory in the pressure application extrusion encapsulation which has proven out. Although in certain type’s of chemical formulations it would not be possible and change the characteristics or destroy it completely. So ultrasound encapsulation has been the standard in most researches. Although some have continued saying that the ultrasound is driving the cargo into the capsule. This process is possible through the use of surrogate molecules but is a carefully controlled method and most carry patents.
However now in standard controlled ultrasound application’s what their seeing now that is not what’s happening. My guess would be because of better visualization of nano particles.
What they found out is that in a controlled setting they actually are splitting the liposome capsule. Laying the capsule open, sending it back to a bilayer sheet and removal of the ultrasound it will spring back to it’s original form, causing the surrounding media to become encapsulated in the core.
This is the latest finding in 2014 and is published in a book costing well over $300 dollars which I don’t believe will hit the top ten any time soon!
Here’s their presentation of this process!
LUV stands for Large unilamellar vesicle. SUV= Small unilamellar vesicle.
Which is what PC liposome composition is. A unilamellar vesicle!
They also go on to explain that using limited preparation of the liposome and a Non commercial or low power, low frequency ultrasound and applying it for an extended time period has some different effects on the production of a capsule and the resulting end product is a different structure all together. This they note is the process that occurs when using non commercial low power cleaner type ultrasounds making attempts to make and encapsulate a liposome.
This type would produce a particle group that would be released in the GI tract and are able to avoid the stomach process. It doesn’t enter the blood stream directly where it can target cells but depends on gut absorption and normal intestinal processing of the drug to reach circulation into the body.
This process open’s the liposome and separate’s it’s bilayer into two different monolayer sheet’s which when they return to their normal shape, form a micelle and a inverse micelle. Micella have the ability of escaping the stomachs acids and continue on thru to the intestines. A Micelle is capable of encapsulating hydrophobic molecules and some hydrophilic molecules. The Inverse Micelle can only encapsulate hydrophilic molecules. So loading them with a water based substance would a have a greater effectiveness in getting it into the system from the intestines faster then a oil based substance due to this difference in acceptance at formation.
It also appears that this process can also be preformed on commercial or lab grade ultrasounds operating on lower powers for extend exposure times. So it appears time is the factor here however at higher powers and longer sonic times, it seems to destroy the liposome completely.
So with all these latest discoveries it appears that although someone may assume they are getting Liposome delivery of whatever and getting the benefit’s of cellular delivery. What their getting is a Micelle mix which has some very different characteristic’s then a true Liposome. Yes! It starts out what is a Liposome but the end product is a different structure all together.
Here’s the pic’s and graphs that show this process.
The term Coalescence in this presentation means!
“The disappearance of the boundary between two particles in contact, followed by changes of shape leading to a reduction of the total surface area.”
This you can see is where the phosolipid molecules heads are pulled together in the layers. The angle and molecular arrangement of the heads on the molecule are what cause the concave and convex formation, eventually leading to a complete circle. In the Bilayer type you would get a Liposome! In a Monolayer type you get either a Micelle or a Inverse Micelle.
Hope this clears up some of the confusion! This helped me understand why there is such misunderstanding as to what does what. Kind of like Apples and Oranges analogy. However in this case were talking about apples that are made out of oranges now that can get to be confusing!!!
To steal ideas from one person is plagiarism. To steal from many is