Nadia Mostafavi

There are some things I do not understand in your question:

• You don't tell us whether you're talking about nematic, smectic, or even cholesteric liquid crystals (LC's)... Or show a single result to support your conjectures... Your statement may be debatable: "...liquid crystal, which is a type of nano particle..."
• Zeta potential (ZP) refers to particulate matter in a continuous phase. I can't understand how you claim to measure the ZP of a pure liquid crystal
• What size do you get for the z-average given that Stokes-Einstein equation is not obeyed for liquid crystal materials? The Brownian motion isn't random in such systems. See the end slides in this webinar (registration required) 48:00 onward:
• The importance of the measurement of diffusion in 2-phase systems
• https://www.malvernpanalytical.com/en/learn/events-and-training/webinars/W150813DiffusionColloidalSuspension.html

Please post more information and your actual results.

Usual reasons are:

• Contamination/dust in the system. What filter did you use to remove large extraneous matter?
• Confusion between intensity, volume, and number distributions. What is your justification for the 100 - 400 nm claimed for the drug size? Are you sure that there is no interaction between the LC and the drug material?

Aggregates of very large size might be formed, which are influencing the z average to very high values even if they are in minor porportion.

You can try to reduce the concentration or filter your dispersions.

In any case, the values of the DLS plot by number % should be more reliable.

Rebeca Fortes-Martín The use of number distributions from DLS is specifically forbidden in the international (ISO and ASTM) standards. The most robust parameters arising from the intensity distribution are the z-average and polydispersity index (PDI).

Nadia Mostafavi It's about 6 weeks since you posed your question and you have not returned to answer the simple questions I posed in my first response. I trust you are well. If you are on vacation then I hope it's a pleasant one.

Hi

First of all, I would like to apologize for my delay in replying. Unfortunately, Research Gate did not allow access to my account due to technical problems. I hope I did not offend you. Also, thank you very much for answering my questions. Alan F Rawle Rebeca Fortes-Martín

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Alan F Rawle

• My goal is actually to make lyotropic cubic liquid crystalline nanoparticles which is also known as Cubosome. Cubosome composition can be tuned to engineer pore sizes or include bioactive lipids, the polymer outer corona can be used for targeting and they are highly stable under physiological conditions.
• Two effective drugs to lower intraocular pressure are loaded into Liquid Crystal.
• DLS results showed numbers like 121, 215,320,... for the size of nanoparticles But the Z-average always showed numbers above 1000. I did not raise any ambiguity about Zeta potential in my question.
• The good news is that I solved this problem by combining the two protocols and spending longer time to better dissolve the drugs in the oil phase and then adding them to the aqueous phase with the help of a thermal magnetic stirrer.

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Rebeca Fortes-Martín

• The proportional amount of Zeta potential showed that there is no possibility of aggregation of particles to a large extent.
• We filtered the formulation before, but the z-average problem was not solved.

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Alan F Rawle

• I apologize again for the delay in responding.Actually, for the last few weeks, I have been trying different possible solutions for my problem. In Iran, we are usually more busy at this time of the year, and there are no holidays until the New Year (beginning of spring).Anyway, thank you very much for your kindness.

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You should use sonication as well as a homogenizer.

I had this problem before and was able to solve it this way.

I will answer if you have any questions.@

Abozar Nasiri Jahrodi Thank you so much for answering my question. I used probe sonicstor as well as a homogenizer before.