Does Nano-Hydroxyapatite Cross the Blood Brain Barrier?

I have been receiving a ton of messages lately about hydroxyapatite (HA), especially nano-HA. I thought this one, in particular, was important to address.

This concern is not completely made up, but it does miss important context.

Most of the studies that I see people cite in this discussion about nano-particles crossing the blood-brain barrier (BBB) involve engineered nanoparticles specifically designed for drug delivery, often under conditions very different from normal toothpaste use.

The two studies mentioned above are one's I often see used when debating this topic, so let's break them down.

Study 1

This study was essentially exploring whether specially prepared hydroxyapatite particles could be used as a way to carry medicine through the bloodstream. In this study the researchers created tiny lab-made particles and mixed them into a liquid solution. They then injected that solution directly into the veins of rats and dogs to see how the body reacted. Importantly, this was not toothpaste and it was not meant to mimic brushing exposure in any way. It was a direct bloodstream injection study designed for medical drug-delivery research.

The researchers found that when very high amounts were injected, the particles could clog tiny blood vessels, which could become dangerous or even fatal. However, at much lower doses, the animals only showed temporary changes in blood markers shortly after injection, and those levels returned to normal within about a day.

The animals were repeatedly exposed to these lower doses over a two-year period, and the researchers did not observe obvious long-term organ damage or chronic side effects. Based on this, the authors suggested that small amounts of these specially prepared hydroxyapatite particles might potentially be useful as a medical drug carrier in the bloodstream.

The Context Missed

This study involved lab-prepared particles being intentionally injected into veins for biomedical research purposes. That is completely different from using nano-hydroxyapatite toothpaste, which is applied topically in the mouth, mostly spit out, and not designed or administered for bloodstream delivery.

Study 2

This paper is basically about scientists trying to figure out how to sneak medicine into the brain. The brain has a super protective filter (the BBB), and most medications can’t easily get through it. So researchers are creating specially designed nanoparticles that are purposely made to cross that barrier and deliver drugs directly into the brain.

To do this, scientists change the size, shape, coating, and electrical charge of the particles to make them more likely to get through the BBB. Some are even coated with proteins or other molecules that basically “trick” the brain into transporting them across.

A lot of these particles are injected directly into the bloodstream, and sometimes researchers even temporarily loosen the blood-brain barrier itself using things like ultrasound or chemicals to help the particles get through. The entire goal of these studies is literally to design nanoparticles that can enter the brain.

The Context Missed

First of all, this paper isn't even about hydroxyapatite nanoparticles (and definitely not toothpaste). It’s a broad review looking at many different kinds of engineered nanoparticles used in medical drug-delivery research, like gold nanoparticles, liposomes, polymer nanoparticles, and other specialized systems.

Both of these studies are very different from using nano-hydroxyapatite toothpaste. Toothpaste is not designed to carry drugs into the brain, is not injected into the bloodstream, and most of it is spit out after brushing. So when people say, “nanoparticles crossed the BBB in a study,” they often leave out the very important detail that many of these particles were intentionally engineered and medically designed to do exactly that.

When It Comes to Toothpaste

Researchers are still studying:

• how different nanoparticle sizes behave biologically

• whether very small particles could theoretically be absorbed systemically

• long-term accumulation potential

• how particle coating, shape, dose, and route of exposure change risk

• Read more about these in my full nHA guide

What We Do Know

For a substance in an oral care product to penetrate the blood brain barrier we have to ask: how is it going to get there? To enter the brain from a toothpaste, a substance would first need to enter systemic circulation, either through the gut or oral mucosa. Gut absorption is unlikely because nano-hydroxyapatite dissolves in the highly acidic environment of the stomach, which has a pH of 1.5–3.5. nHA begins dissolving at a pH of 4, meaning it would likely break down before ever reaching the bloodstream. And studies show it most likely does not penetrate the oral epithelium either.

Will future research show that it actually can via properly used toothpaste route? Sure, maybe. But right now we can only go off of what we know.

Research on Topical Use in Oral Care

When it comes to oral care specifically, available research paints a very different picture. A key study evaluating toothpaste containing 10% nano-hydroxyapatite applied the substance directly to oral mucosa and found no penetration through the oral epithelium. This means the nHA remained on the surface and did not enter the bloodstream or systemic circulation. Furthermore, applying 10% nHA (50 nm particle size) to both keratinized and non-keratinized oral tissues for 24 hours found no evidence of tissue penetration, supporting the conclusion that systemic absorption through the mouth is highly unlikely.

When looking at research it's important to understand the full context behind the findings before trying to compare to oral care products: Is the particle shape known? Do they give the concentration? What was the method of delivery? How was the nHA prepared/for what purpose? What is specifically engineered to cross the BBB?

Ready to deep dive even further?

Let's take a look at the claims that HA turns teeth gray and causes cavities.