PURE ZETA: PART TWO; Debye length and zeta potential.
There are two main equations used in colloidal systems to estimate zeta potential.
Debye length is part of those equations, and, IT CAN CHANGE!
This is part of the reason the zeta potential can change!
2/ When I calculated a zeta potential in the past, I used incorrect numbers intentionally to see who was really paying attention, but also, why any kind of measurement is only for that one moment in time, around the surroundings it is in, at that time. The interaction can change.
3/ Here is the previously discussed Smoluchowski Equation (I am going to pull each one apart, explain each unit of measurement, and why it is important, the best that I can, in this little box (that is not adequate at AL), on "X".
ζ=2⋅η⋅Eμ⋅ε
That is the Smoluchowski Equation
4/ Where:
ζ is the zeta potential.
μ is the electrophoretic mobility of the particle.
ε is the dielectric constant of the medium.
η is the viscosity of the medium.
E is the applied electric field.
(this is going to get daunting, so it will be broken into many many threads)
5/ Here is the Henry equation discussed in the last thread:
ζ=3⋅η⋅rH2⋅μ⋅ε
Where:
ζ =zeta potential.
μ = electrophoretic mobility the particle.
ε = dielectric constant of the medium.
η = viscosity of the medium.
rH= is the hydrodynamic radius of the particle.
It's OK.
6/ It looks like a lot but it is plug and play algebra most of it. It just looks like it will melt your brain, but if you slowly take things apart, and just add in numbers, it's going to be OK. Or not.
Now, Debye length, named after the Dutch physical chemist Peter Debye,
7/is a parameter in electrochemistry and colloid science. It's also known as the Debye-Hückel screening length. The Debye length (λ_D) is the thickness of the electrical double layer around charged particles in a solution.
In simpler terms,
6/When particles in liquid have electric charge on their surface, they create "cloud" of charge around them. The Debye length is thick or thin this cloud is. If the Debye length is short, is the cloud is close to the particle, and if it's long, the cloud extends farther away.
7/ that little arrow in the clouded region above, that is the Debye length. Debye length tells us how far the effects of these charges reach and how they influence things like particle movement and interactions with other charged particles--like an LNP would interact i the body.
8/ Debye length is more of a concern when calculating zeta potential with the Henry equation, because they are not quite spherical, and it is more indirect of a concern in the Smoluchowski equation, but it is still important. The thing is, Debye length, CAN CHANGE!
9/Debye length (λ_D) can change depending on ionic strength of solution and properties of electrolytes present. Ionic strength refers to the concentration of charged ions (like sodium and chloride) in the solution.
The Debye length can change in the context of liposomes
10/ interacting in a human body with a drug in the following ways:
en a liposome-based drug is injected into the bloodstream, the ionic strength of the surrounding environment can vary. Blood contains various ions, and their concentrations can fluctuate due to factors like
11/hydration, diet, and medical conditions.
Effect on λ_D: An increase in ionic strength (higher ion concentration) tends to shorten the Debye length, while a decrease in ionic strength (lower ion concentration) lengthens it. So, the Debye length around liposomes in
12/bloodstream can change as the body's ionic conditions change.
In the bloodstream, liposomes may encounter proteins like albumin, which can adsorb onto their surfaces, forming a "protein corona." This protein corona alters the surface chemistry of liposomes.
13/ The adsorption of proteins can change the composition of ions in the vicinity of the liposomes, which, in turn, affects the Debye length. Depending on the nature and extent of protein binding, the Debye length may increase or decrease. The PEGylated lipid is supposed to
14/ inhibit proteins in the blood and in other areas from the body to sticking to it. The PEG creates a steric barrier around the LNP (umbrella reference in other thread) from bouncing into other things, but this does not mean it will not interact, or that charge cannot change.
15/Liposomes/ LNP may be designed to release their drug payload in specific body compartments with different pH levels. For instance, some liposomes release drugs in the slightly acidic environment of tumor tissue.
16/changes can influence the ionization of molecules in the solution. Alterations in ionization can, in turn, impact the Debye length. In regions with different pH values, the Debye length around liposomes can vary accordingly.
17/In summary, Debye length can change as ionic strength, protein interactions, and pH conditions in the body change. Variations occur when liposomes interact w/ different bodily fluids/ tissues, and they can affect the behavior and stability of liposomal drug delivery systems.
18/ Therefore, even with this one aspect that involves the charge on the surface of an LNP, things can change. Nothing exists in a vacuum.
When Pfizer took this measurement, it was in a lab, not in a human body. And even after it enters, it could change. All of it.