Tri-Domain Was Called Impossible. The Papers That “Prove” It Actually Prove NanoBase™ Right.

Every so often someone points at NanoBase™, cites a paper, and says a tri-domain carrier cannot exist. They are usually holding a real citation. Here is the part they miss: the papers are correct, and not one of them is about NanoBase™. Read them properly and they describe exactly why the architecture works.

Let us do that, with the citations on the table.

The objection, and where it comes from

There are two classic sources people reach for.

The first is Israelachvili, Mitchell and Ninham, 1976, the paper that gave colloid science the molecular packing parameter (J. Chem. Soc. Faraday Trans. 2, 72, 1525, DOI 10.1039/F29767201525). It links molecular geometry and thermodynamics to predict the size and shape of the aggregate a surfactant forms. Read quickly, it becomes: one surfactant geometry gives one equilibrium morphology, so you cannot have three architectures at once.

The second is the nano-emulsion stability literature, canonically Tadros, Izquierdo, Esquena and Solans, 2004 (Adv. Colloid Interface Sci. 108-109, 303, DOI 10.1016/j.cis.2003.10.023). Its point, repeated across the field: nanoemulsions are thermodynamically unstable, unlike thermodynamically stable microemulsions. Given infinite time, they separate.

Both are true. And NanoBase™ does not argue with either of them. That is the whole trick.

We concede the law. Every word of it.

NanoBase™ is a nanoemulsion-class architecture, and the class is well defined. As McClements and Jafari put it in 2018, nanoemulsions “are not thermodynamically stable systems and cannot form spontaneously without energy input” (General Aspects of Nanoemulsions and Their Formulation, DOI 10.1016/B978-0-12-811838-2.00001-1).

We agree completely. NanoBase™ is not thermodynamically stable. It does not form on its own. It is built with energy input. If the objection is “this is not a spontaneous equilibrium structure,” the answer is: correct, and it was never claimed to be.

The packing-parameter objection has the same shape. Israelachvili’s framework predicts the equilibrium aggregate a single amphiphile forms when left alone. NanoBase™ is not a single amphiphile left alone. It is a multi-surfactant, multi-population system held out of equilibrium on purpose. The 1976 paper says nothing about that case, because that case is not what it modeled.

So the critics are answering a question no one asked: what does a mixed system become if you leave it alone? The honest answer is one interface. We asked a different question: what does it do if you never leave it alone?

The answer is kinetics, and the same literature says so

Thermodynamics decides the destination. Kinetics decides whether the system ever arrives. And arrival time is a design variable.

Gupta, Eral, Hatton and Doyle, in the most-cited modern formation review (Soft Matter 2016, 12, 2826, DOI 10.1039/C5SM02958A), state it directly: nanoemulsions are thermodynamically unstable, yet because of their small size they can remain kinetically stable over long time scales. The same review even warns that critics routinely confuse nanoemulsions with the thermodynamically stable microemulsions that form spontaneously, which is precisely the confusion behind the “can’t exist” claim.

The mechanism is not mysterious, and it is named in the literature. A 2024 study in Langmuir describes nanoemulsions being “kinetically stabilized by increasing the energy barrier for droplet coalescence” (DOI 10.1021/acs.langmuir.4c02997). Raise the barrier high enough and the thermodynamically favored collapse simply never happens on any timescale a product lives through.

And this is settled in cosmetic terms specifically. A 2024 review of cosmetic nanoemulsions (IntechOpen, DOI 10.5772/intechopen.1004740) spells out that thermodynamic and kinetic stability are independent axes: a substantial kinetic barrier can hold a system stable even when destabilization is thermodynamically favorable, so a system can be thermodynamically unstable yet kinetically stable. That sentence is the NanoBase™ claim, written by someone with no stake in NanoBase™.

Even the newest comparative review, in Advances in Colloid and Interface Science (2026, “Microemulsions versus nanoemulsions”), defines the whole class this way: nanoemulsions are thermodynamically unstable but kinetically stable dispersions of droplets below 200 nm. That is not a description of a problem. It is the definition of the category NanoBase™ was engineered to master.

What actually holds the three domains apart

The barrier the literature calls for is what we call the electrostatic wall, and it is textbook DLVO. Colloidal particles feel van der Waals attraction pulling them toward collapse and electrostatic repulsion pushing them apart. NanoBase™ is engineered so repulsion wins. The domains are designed to carry like charge, so they resist the approach and fusion that thermodynamics is trying to drive. The barrier is raised, and the metastable tri-domain population is held in place.

The nanoemulsion stays a nanoemulsion. The vesicle stays a vesicle. The micelle stays a micelle. Not because we repealed thermodynamics, but because we walled off the road to the single-interface minimum. That is why we call the electrostatic wall the design principle of the architecture, not a feature.

And this is the one thing to keep straight. Tri-domain does not mean three thermodynamic phases crammed into one droplet at equilibrium. It means three coexisting populations under kinetic control, each a stabilization axis in its own right. The wider, structured size distribution a genuine tri-domain carrier reads, against the roughly 185 nm design target we characterize in-house by multi-angle dynamic light scattering, is not noise. It is the fingerprint of three populations holding.

The reframe, and the point

Legacy HLB chemistry, the 1949 surfactant-matching scheme still running most of the category, lives exactly at the equilibrium these papers describe: one interface, one compromise for every payload at once. It is comfortable because it is the collapsed state, sold as a finished product. That comfort is also its ceiling.

NanoBase™ lives above that equilibrium, in the metastable state, held there by an engineered barrier the physics literature already told everyone how to build. The people who called tri-domain impossible were not wrong about equilibrium. They just never asked what happens when a system is designed never to reach it.

Impossible at equilibrium. Engineered in practice. That is the difference between the standard the industry inherited and the standard it is moving toward.

References

• Israelachvili, Mitchell and Ninham (1976). Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. J. Chem. Soc. Faraday Trans. 2, 72, 1525. https://doi.org/10.1039/F29767201525

• Tadros, Izquierdo, Esquena and Solans (2004). Formation and stability of nano-emulsions. Adv. Colloid Interface Sci. 108-109, 303. https://doi.org/10.1016/j.cis.2003.10.023

• Gupta, Eral, Hatton and Doyle (2016). Nanoemulsions: formation, properties and applications. Soft Matter 12, 2826. https://doi.org/10.1039/C5SM02958A

• McClements and Jafari (2018). General Aspects of Nanoemulsions and Their Formulation. In Nanoemulsions: Formulation, Applications, and Characterization. https://doi.org/10.1016/B978-0-12-811838-2.00001-1

• Phase-Change Nanoemulsions for Thermal Energy Storage (2024). Langmuir 40, 21814. https://doi.org/10.1021/acs.langmuir.4c02997

• Ajayi (2024). Thermodynamic and Kinetic Stability of Cosmetic Nanoemulsions. IntechOpen. https://doi.org/10.5772/intechopen.1004740

• Microemulsions versus nanoemulsions: A comparative overview (2026). Advances in Colloid and Interface Science. PMID 41905284.

• Pensive Beauty. NanoBase™ technical record. Zenodo. https://zenodo.org/records/18616576