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Nanoparticles are a viable method of delivering highly specified medicines. Therefore, understanding the effects to prevent them from aggregating in liquids is vital. This means that it is necessary to investigate the electrokinetic potential they generate — the zeta potential.
The use of nanoparticles represents a significant breakthrough in medicine due to their ability to deliver drugs, light, and heat to specifically targeted cells. For this medical revolution to proceed, researchers need an efficient way to introduce nanoparticles —particles smaller than 100 nanometers in diameter — into a patient’s system. One way of achieving this smart drug delivery is in a colloid suspension — a liquid with other liquids or solids suspended throughout it — but, this obviously means that the liquid must be tightly controlled and not allowed to change states.
One particular concern with a colloid solution is the need to prevent ‘clumping’ of one substance within the other. Preventing the aggregation of nanoparticles, or any other substance, within a colloid solution and keeping it stable requires an understanding of the electrical potential at play between the particles and their medium as they move through it. Additionally, many other properties of a colloidal solution are determined by the electric potentials at work within it. Within such colloid suspensions, this electrokinetic potential is more accurately known as zeta potential — and understanding it is of vital importance.
What is Zeta Potential?
The earliest theory for calculating Zeta potential from experimental data was developed by Marian Smoluchowski in 1903. It remains the most well-known and widely used method for calculating zeta potential.
A small charge at the surface of a nanoparticle draws a thin layer of ions with an opposite charge to the layer of ions that naturally coats it. This results in a double layer of ions which the nanoparticle carries with it as it moves through the liquid. This means we can view the nanoparticle moving through a dispersion medium as being coated with a stationary layer of that medium. The electrical potential at the boundary of this double layer, between the layer grabbed by the nanoparticle and the solution, is the zeta potential.
The idea of this stationary plate where the double layer slides past the medium enveloping the nanoparticle is referred to as the surface of sheer and in many ways, it can be considered almost imaginary. The real slipping surface is likely to be almost constantly fluctuating, but as these tiny fluctuations occur on a short time scale in comparison to the duration of a measurement, an abstraction is perfectly permissible. It’s just one of the simplifications that scientists must make to model such an incredibly complex system with a lot of forces at play.
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Estimating the zeta potential — for which values are usually given in volts (V) or microvolts (mV) — gives researchers a good idea of how stable a colloidal solution is. The zeta potential generally ranges between +100mV and -100mV. Nanoparticles that demonstrate a zeta potential with values above 30mV display high stability. Likewise, nanoparticles with a zeta potential less than -30mV also resist aggregation.
In contrast to this, nanoparticles with zeta potentials of below 25mV and above -25mV find it incredibly difficult to resist the forces that work to make them conglomerate. This means they have a weakness to the effects of interparticle forces that cause clumping, such as van der Waals forces and hydrogen bonding. As such, the key to establishing a stable colloid liquid or emulsion that will not begin to gather flakes within it is understanding the zeta potential at the surfaces of the nanoparticles floating within it.
The most important factor that researchers have thus far pinpointed in controlling zeta potential is the pH factor of the medium in which the nanoparticles diffuse. In addition to this, perhaps unsurprisingly, the strength of the ionic concentration can also have a major effect. A great deal of research has gone into the improvement of zeta potential and thus the stability of colloid solutions, finding that adding impurities to a colloid can strongly influence zeta potential.
Measuring Zeta Potential
Unfortunately, zeta potential is not measurable directly, but chemists can measure the effects it induces as the nanoparticle moves through the medium it inhabits. These are broadly categorized as electrokinetic effects: electrophoresis, electro-osmosis, streaming potential, and sedimentation potential.
This family of effects is found in fluids that contain particles of other substances — solids, liquids, or even gases — and arises as a result of the double layer of ions sliding past the medium. This movement is caused by the application of an external force, be it electric, gravitational, or caused by a pressure gradient.
There are also electroacoustic effects, such as colloid vibration current and electric sonic amplitude, caused by zeta potential which is commonly used to determine its characteristics.
Even with these effects, it is still very difficult to garner an estimation of the zeta potential. Even when utilizing mathematical tools such as vector calculus and solving the resulting differential equations with powerful computers, significant simplifications have to be made in order to model real-world experiments. Many of these are common shortcuts that will be familiar to physicists, for example treating the nanoparticle as a perfect sphere or a flat ‘plate’ where it meets the medium.
As these models become more precise and researchers begin to narrow down the effects at the surface of the nanoparticle, our understanding of how to deliver increasingly complex and useful medicines grows in sync.
References and Further Reading
Hunter. R. J, ‘Zeta Potential in Colloid Science: Principles and Applications,’ Academic Press Limited, (1981)
Gupta. V, Trivedi. P, ‘In Vito and in vivo characterization of pharmaceutical topical nanocarriers containing anticancer drugs for skin cancer treatment,’ Lipid Nanocarriers for Drug Targeting, (2018)
Kumar. A, Dixit. C. K, ‘Methods for characterization of nanoparticles,’ Advances in Nanomedicine for Delivery of Therapeutic Nucleic Acids, (2017)
Joseph. E, Singhvi. G, ‘Multifunctional nanocrystals for cancer therapy: a potential nanocarrier,’ Nanomaterials for Drug Delivery and Therapy, (2019)
Pavan M. V. R, Barron A.R, ‘Zeta Potential Analysis,’ Libre Texts: Chemistry, (2010)
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