I am using the mother buffer so it does not destabilize the formulation. Yet I am getting negative results. One possible reason could be the charge of the buffer itself. Any ideas on other possible reasons pertaining to the liposomes itself??
What do you mean by "cationic empty liposomes"? Are you using phosphatidyl lipids? If so, these are zwitterionic and so the zeta potential will very likely be pH-dependent. What is the composition of your buffer?
What's the exact composition of your liposomes? Are you diluting the sample in order to read zeta potential? Are you using a Malvern equipment? if so, what's the quality fo the measurement? John Francis Miller is right when he says that some cationic lipids are very pH-dependent.
I don't have all the information to the compositions of the lipid in the liposome. From what I know, there are four lipids and one or more are phospatidyl lipids. Also, I am using the original formulation buffer to make dilutions which itself has some negative charge which could be why I am getting negative zeta. Any suggestions on how to overcome this or ways to stabilize the pH?
You can perform different measurements with your original buffer but change the pH, try for example 5, 7 and 9, so you can see if your liposomes change zeta potential with pH. On the other hand, you can use for example water, to test if your buffer has the accurate ionic strenght.
Also, are you liposomes stable? Size is stable for what period of time? Maybe you have changes in zeta potential due to aggregation or chemical instability.