Hi, I'm currently in the work of making lipid nanoparticles where I'm using cationic lipid molecules to attract anionic mRNA to make the particles. Currently, the mixture is acidic when I make the particles, however, to remove ethanol, the pH needs to be adjusted to 7 before I can use a buffer exchange system at larger scales. When I adjust to pH 7, the ethanol concentration is reduced, but the particle size increases.
My question is regarding the effect of ethanol on the 'apparent' pH.
After I make the particles, the pH is around 6.6, but the ethanol concentration is 25%, I've found that ethanol increases the apparent pH so I'm assuming the true pH is lower, perhaps 6-6.2.
The pKa of the mRNA is 6.4, I'm thinking that due to the effect of ethanol on the pH reading, when I adjust to pH 7, the actual pH is 6.4, and I'm seeing particle growth due to the maximum number of mRNA molecules attaching to the lipid.
Does anyone have any insight on this?