I work with a 2 similar but structurally different PEGylated polymeric nanoparticles encapsulating a traditional chemotherapeutic drug. The nanoparticles are developed to be administered orally. Preliminary efficacy studies shows good tumor control compared to free drug for both nanoparticle formulation. But size distribution studies of the drug encapsulated nanoparticles shows 2 peaks (suggesting breakdown of nanoparticles at acidic gastric pH), implying drug release as soon as nanoparticles reach stomach for one and significant difference in size (small size about 60 nm at pH 2, 120 nm at pH 7 and 150 nm size at pH 8) with a single peak for the other. What does these results imply? Why is there a size difference with pH.
Hi Sasidharan,
Polymeric compounds in general swells or shrinks depending the conditions they are into. I could see one thing from your explanation that size of your nanoparticles increases by amount of decreased amount of protons. This effect is called as pH responsiveness of your particles. I would encourage you to do some lit search on pH-responsive polymers or hydrogels. The drug is released due to expansion of polymeric network at increased pH possibly due to some form of chemical reaction with the functional group of polymeric material.
Please do check the isoelectric point of your polymer.
Probably you will find the answer after you explore some more on your polymer.
Hi,
All the answers above are correct but not necessarily correct in your case. I assume that you measure the size with DLS, which means you actually measure the hydrodynamic diameter of your NP. This means that as the pH is changing then the interaction with the medium is changing which seem to be increasing with pH. This means the interaction with solvent increases and the "hydrodynamic cage" the medium creates is increasing and that is why it looks like it's getting "bigger" when actually it is just the same size. If you do use DLS please make sure that you remember to adjust the medium parameters from the default "water", otherwise that will cause another error into your readings.
Good luck!
Hi Parthiv, So far we did not think that our nanoparticles has pH responsiveness. Maybe you are right. Thank you for yor suggestion.
Hi Roni,
Yes i did measure the size by DLS. And i did change the medium its viscosity and refractive idex at 37degrees before i did the measurements. I think there is no other way to measure the size change in medium with pH. Pls share if you know of any methods to check the change in size with pH of the medium.
Hi Sasidharan,
There are other methods to measure size non are specific for pH effect just like DLS is not. You have the qualitative options like SEM or TEM and you can make it quantative and that's a lot of work. You can also use the similar method to DLS which is by laser particle tracking (thus method actually "watch" your particles) or using fluid dynamics particle measurements too.
Roni
1. Extreme acidic pH can induce hydrolysis of some polymers which might affect the size and stability of the nanoparticles.
2. The pH can influence the hydrophobicity of the polymer or drug. (please see the article attached)
3. The pH can affect the charge on the polymer and hence the size. The pKa of the polymer and drug can answer why there is an increase in size when the pH is basic.
More details on the nature of the polymer and drug can be helpful.
Explanation based on Electrostatic Interaction: Assuming it is a cationic polymer,
When using cationic polymers, the charge density of polymers increases in acidic pH. This increase in charge can either increase or decrease the size of the nanoparticles based on the counter-ions (e.g. drug, salt) present in the medium.
Increase in Size: If there is no counter-ions to neutralize the charge, then the repulsive force between the chains of the polymer can lead to formation of less compact nanoparticles. Hence increase in size in acidic pH.
Decrease in Size: If there drug acts as a counter-ion, then there would be stronger interaction between the drug and polymer, resulting in more compact nanoparticles.
The vice versa would be true for negatively charged polymers.
https://www.researchgate.net/file.PostFileLoader.html?id=56b792407c1920b3f08b45d4&assetKey=AS%3A326567235473408%401454871104283
When you have REALLY (?) a charged polymer as the (core ?) component of your nanoparticles, from your experimental finding I guess it should be a negatively charged one.
ASSUMING it is such an anionic polymer (core of your nanoparticles) and assuming you have carboxyl groups as charged moieties, increase of pH value means increasing the charge density of the polymer, which means increased self repulsion of the polymer segments, which could mean increase in size but decrease of local density due to chain expansion within the polymer particle.
Additional salt (coions) decreases the Debye length (electrostatic reach), which is around 1 nm for 0.1M (assuming monovalent salt), which means that salt would reduce the chain expansion due to electrostatic shielding and thus decrease particle size.
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