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Function of the Oral Mucosa and its Permeability
Discover how the oral mucosa functions, its permeability, and its protective barrier. Learn about its interaction with surfactants, particles, and other substances to understand its importance in oral health.
SCIENCE
Luigi Cellini
9/28/20268 min read
Prefer to read this article in Spanish? Read the Spanish version →
The oral mucosa: a living barrier
When we think about brushing our teeth, we think mainly about our teeth.
But toothpaste does not come into contact with them alone.
During brushing, its components are distributed over the tongue, the gums, the cheeks and other soft surfaces of the mouth.
And those surfaces are not inert.
They are made up of living tissues that play a part in protecting the body and that, at the same time, can allow certain substances to pass through.
That is why, before asking what effect a particular ingredient may have, there is a more basic question:
what happens when a substance comes into contact with the oral mucosa?
What is the oral mucosa?
The oral mucosa is the tissue that lines much of the inside of our mouth.
It is not a uniform surface.
Some regions, such as the gums and the hard palate, are keratinised and present a relatively poorly permeable barrier.
Other non-keratinised areas, such as the mucosa of the cheeks, are more permeable.
The scientific literature has been describing these differences for decades.
A classic review on the permeability of the oral mucosa points out precisely that it should not be regarded as a uniformly permeable tissue: keratinised regions are among the least permeable and non-keratinised lining areas among the most permeable.
Scientific study: The permeability of oral mucosa [1]
Therefore, speaking of "the mouth" as if its entire surface reacted in the same way would be an oversimplification.
A barrier, but not an impermeable wall
The barrier function of the mucosa is essential.
But a biological barrier does not mean an absolutely impermeable wall.
In fact, the oral mucosa has an abundant blood supply and possesses characteristics that allow the absorption of certain molecules. This is precisely why it has been studied for decades as a possible route for administering medicines both locally and systemically [12].
This introduces a fundamental distinction:
coming into contact with the mucosa, penetrating the epithelium, crossing the mucosa completely and reaching the systemic circulation are not the same thing [13].
Demonstrating one of these does not automatically demonstrate the next.
This distinction will be important throughout this page.
Above the mucosa there is another barrier: saliva
Protection does not begin solely in the cells of the epithelium.
Saliva contains mucins and numerous biomolecules that form coatings over the oral surfaces.
Mucins are large glycoproteins that help to create a protective layer over moist epithelia and play important roles in defence against the environment and microorganisms.
Over the oral mucosa itself there is what is known as the mucosal pellicle.
Among its components are salivary mucins and mucins associated with cell membranes. This pellicle is considered to play a part, among other functions, in the lubrication and preservation of moisture on the oral surface.
Scientific review: The mucosal pellicle – An underestimated factor in oral physiology [2].
This slightly changes the way we imagine the mouth:
the oral surface is not simply a tissue that we have to clean. It is an ecosystem protected by biological structures that the body itself produces.
Can the permeability of the mucosa be modified?
Yes.
And we know that it can be done because there is an entire field of pharmaceutical research dedicated precisely to achieving it.
One of the problems with administering medicines through the oral mucosa is that its barrier function limits the penetration of many molecules.
To overcome this limitation, substances known as permeation enhancers, or permeation promoters, have been studied.
Their aim is to modify the properties of the barrier temporarily in order to facilitate the passage of certain substances.
Among the different classes of substances investigated for increasing buccal permeation are:
surfactants, bile salts, fatty acids, chelating agents, cyclodextrins and chitosan.
Scientific review: Drug permeation enhancement via buccal route: possibilities and limitations [3]
This does not mean that any surfactant used at any concentration automatically produces relevant systemic absorption.
It means something far more precise:
the permeability of the oral mucosa can be modified chemically, and surfactants are among the substances studied for their ability to modify it.
How can this permeability be increased?
The mechanism is not necessarily a single one.
A review dedicated specifically to buccal penetration enhancers describes various possible mechanisms, including changes in the partitioning of substances towards the epithelium, extraction of intercellular lipids, interaction with protein domains of the epithelium or increased retention of a substance on the mucosal surface.
Scientific review: Buccal penetration enhancers — how do they really work? [4]
But an important problem arises here.
If we modify a barrier to facilitate the passage of a substance, we must also ask ourselves what effect that modification has on the tissue itself.
The pharmaceutical literature recognises precisely this balance: a useful permeation enhancer should increase permeability without producing toxicity or permanent damage to the membrane. Irritation, membrane damage and toxicity constitute known limitations in the development of these substances [14].
What about the surfactants in toothpastes?
Here the question ceases to be purely theoretical.
Sodium lauryl sulfate (SLS) is a surfactant used in oral hygiene products and has been studied specifically for its effects on the mucosa.
An experiment carried out on human oral mucosa studied the effect of SLS, alone and combined with other components, on the barrier properties of the tissue.
After 15 minutes of treatment with SLS, the researchers observed a significant increase in water permeability compared with the control tissue.
Scientific study: The effect of sodium lauryl sulphate, triclosan and zinc on the permeability of normal oral mucosa [5]
This does not prove either that daily brushing produces a dangerous systemic absorption of the ingredients of a toothpaste.
The study demonstrates something more limited, but relevant:
under the experimental conditions studied, SLS modified a barrier property of the human oral mucosa.
Can it also affect the integrity of the surface?
Other experiments have studied the desquamation of the mucosa.
In a small double-blind crossover study, ten participants used toothpastes with SLS concentrations ranging from 0 to 1.5%.
The toothpaste without SLS did not produce the reaction studied, whereas the toothpaste with 1.5% SLS caused desquamation in 60% of the participants under the experimental conditions used.
Scientific study: Desquamative effect of sodium lauryl sulfate on oral mucosa [6]
Another double-blind study compared toothpastes with SLS, cocoamidopropyl betaine (CAPB) and a detergent-free paste.
Many more desquamation reactions were observed during the periods of SLS use.
But the authors themselves introduced a particularly important limitation: the experimental model used did not directly reproduce normal brushing with toothpaste.
Scientific study: Oral mucosal desquamation caused by two toothpaste detergents in an experimental model [7].
That limitation matters.
An experimental observation must not automatically become a statement about damage during daily use.
And what if the mucosa is already altered?
This question deserves special attention.
A review on topical medicines for mucosal diseases points out that permeability varies with the thickness and degree of keratinisation of the epithelium.
It also points out that when the barrier is lost through ulceration or erosion, the diffusion of medicines into the tissue may be faster than through an intact mucosa.
This means that we cannot always extrapolate data obtained on a healthy, intact mucosa to a damaged mucosa.
There is also specific clinical research on SLS in people with recurrent aphthous stomatitis.
A randomised clinical trial with 90 participants found no significant differences in the number of ulcers or episodes between the toothpastes studied, but observed a shorter duration of ulcers and less pain during the period of use of the toothpaste without SLS [15].
Clinical trial: Effect of sodium lauryl sulfate on recurrent aphthous stomatitis [8].
A subsequent systematic review has examined together the available trials on toothpastes with and without SLS in people with this condition.
View the systematic review on PubMed
Therefore, it would also be incorrect simply to state that "SLS causes mouth ulcers" [9].
The available evidence allows a far more prudent statement: there are effects of detergents on the mucosa and clinical results that justify studying especially their use when the integrity of that mucosa is compromised.
WHAT HAPPENS WITH PARTICLES AND NANOPARTICLES?
Here we must again separate different concepts.
A nanoparticle that comes into contact with the mucosa does not necessarily cross it.
And a particle that penetrates partially into a tissue does not necessarily reach the systemic circulation.
However, the possibility of using nanoparticles to improve the buccal administration of medicines is currently an active area of research. Systems designed precisely to increase the retention, penetration or uptake of substances via this route are being studied.
There is also specific experimental research on the buccal mucosa as a possible route for the uptake of titanium dioxide nanoparticles. The researchers themselves point out that, when nanoparticles enter the oral cavity through oral products or other sources, one of the questions is whether they interact with the mucosa or are simply swallowed [16].
Scientific study: The buccal mucosa as a route for TiO2 nanoparticle uptake [10].
This does not allow the result to be generalised to any particle or to any ingredient of a toothpaste.
Size, chemical composition, shape, surface, aggregation, concentration and time of exposure can radically modify their behaviour.
That is why "it contains small particles" and "those particles cross the mucosa and reach the body" are completely different statements.
TIME OF CONTACT ALSO MATTERS
Biological exposure does not depend solely on which substance we use.
It also depends on:
concentration × time of contact × frequency of exposure × characteristics of the tissue.
And in the mouth there is also a dynamic system.
Saliva flows, surfaces are renewed, the epithelium desquamates and the tongue, swallowing and movements of the mouth remove materials from the surface [17].
In fact, these mechanisms constitute precisely one of the obstacles that pharmaceutical technology tries to overcome when it seeks to keep a medicine on the mucosa long enough for it to be absorbed.
That is why we cannot equate a prolonged exposure experiment with a few minutes of brushing either.
A QUESTION THAT CHANGES THE PERSPECTIVE
We normally evaluate a toothpaste by asking ourselves:
does it clean the teeth?
But the anatomy and physiology of the mouth raise another question.
During brushing we do not expose only a mineral surface.
We also expose a living barrier, covered by saliva and mucins, populated by microorganisms and made up of tissues with different degrees of permeability [11].
We know that this permeability can be modified.
We know that certain substances are studied precisely in order to achieve this.
And we know that some surfactants used in oral hygiene products have produced changes in permeability, irritation or desquamation under certain experimental conditions.
What we do not know from these studies is that the habitual use of any conventional toothpaste necessarily produces systemic damage.
Confusing the two statements would go beyond the evidence.
WHAT WE KNOW AND WHAT WE DO NOT YET KNOW
The available evidence allows several points to be established fairly clearly.
The oral mucosa is a selective biological barrier, not an impermeable surface. Its permeability varies according to the region.
The mucosal surface is also protected by salivary components and mucins that play a part in its defence and lubrication.
Pharmaceutical science demonstrates that oral permeability can be deliberately modified and that there are substances — including certain surfactants — studied as permeation enhancers.
And there are experiments on SLS that have observed modifications of the permeability and of the surface integrity of the mucosa under certain conditions.
What these data do not allow us to assert is that every ingredient that comes into contact with the mouth is absorbed, that every modification of the barrier produces damage, or that the experimental effects observed are automatically equivalent to those produced by daily brushing.
Between contact, penetration, absorption and systemic effect there are several steps that must be demonstrated separately.
And perhaps that is precisely the most important question.
When we use a product every day, should we ask ourselves only what it does to our teeth?
Or also what it does to the living barrier that surrounds them?
SUPPLEMENTARY SOURCES CITED IN THE TEXT
The mucosal pellicle – An underestimated factor in oral physiology
Drug permeation enhancement via buccal route: possibilities and limitations
The effect of sodium lauryl sulphate, triclosan and zinc on the permeability of normal oral mucosa
Desquamative effect of sodium lauryl sulfate on oral mucosa. A preliminary study
Oral mucosal desquamation caused by two toothpaste detergents in an experimental model
Revisión sistemática sobre SLS y estomatitis aftosa recurrente
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