Artificial Salivas: Why Are They Not More Useful?

Surface tension (mN/m)
WMS
1:14
1:6
1:1
Artificial saliva
BioXtra
50
55
50
35
45
Saliveze
50
50
55
55
60
Saliva Orthana
50
50
45
45
45
Biotene
50
n/aa
n/aa
n/aa
30
aFor Biotene mixed with WMS, no values could be obtained as the sample constantly wicked – implying a very low surface tension
Most salivary lubrication of surfaces is provided by salivary mucins which act in solution to provide hydrodynamic lubrication in the mixed regime [25] but also absorbs to mucosa [10] to provide a boundary-type lubrication. Other proteins in saliva such as statherin [14], cystatin [3] and albumin [15] may also provide a boundary or close contact-type lubrication. Although most artificial salivas are viscous which will contribute to hydrodynamic lubrication, none of the current artificial salivas mimic the pellicle-forming properties of salivas by binding to the mucosa. The lack of binding also increases the speed at which the artificial salivas are cleared from the mouth by swallowing. This could be a major reason why artificial salivas are not perceived to have a lasting beneficial effect. The lack of substantivity may be addressed by the use of hydrogels which can adhere to the mucosa as reviewed recently [28].

Systems to Model the Efficacy of Artificial Salivas

One problem in developing artificial salivas is the lack of a suitable in vitro model; most salivas have to be tested in vivo using expensive, time-consuming human studies that often only measure the perception of dryness. Whilst these studies directly address the key symptom of oral dryness, they give no information on the mechanism of symptom alleviation and so are highly susceptible to the placebo effect. For dry mouth patients putting any liquid into the mouth probably has a beneficial effect. Consequently the correct control using a double crossover study should be used, but these are costly and do not allow many artificial salivas to be tested. However there are not many useful in vitro systems that can mimic the oral mucosa. Ex vivo pig’s tongue has been used [24] but obviously has some differences compared to the human tongue. Cell models of the oral mucosa are becoming available [7] although they are expensive and may not resemble all the structural qualities of the oral mucosa. Instead investigators have used synthetic mimetics to model the oral surface including glass/silica [1] and PDMS [31].

Composition of Artificial Salivas

For the artificial salivas commonly available via the NHS (see www.​medicinesresourc​es.​nhs.​uk) in the UK or over the counter in most countries, the main polymer is either carboxymethylcellulose or xanthan gum. Only Saliva Orthana uses a biological base – purified mucin extracted from pig gastric mucosa (see Table 11.2). All these polymers are present at high concentrations to create a solution which is quite viscous [30]. The viscosity of the solutions is beneficial and reflects the viscosity of whole mouth saliva, aids the lubrication of tissues and slows its removal from the mouth by swallowing. In addition, to these thickening agents, all artificial salivas need to have preservatives added, so the product can be stored on the shelf. The potentially harmful effects of swallowing large amounts of these preservatives are discussed in an earlier chapter by Prof Ligtenberg. This appears to be an unavoidable effect of taking artificial salivas; however, it has to be noted that adverse side effects of artificial salivas are very uncommon. Most patients seem to stop using these products because of the cost (the same as a prescription charge in the UK) and/or because they do not provide sufficient relief rather than any perceived side effect from the consumption of the product.

Table 11.2

The components of artificial salivas
Name
Bulk polymer
Actives
Preservatives
Others
BioXtra
Hydroxyethylcellulose
Lactoferrin, lactoperoxidase lysozyme
Potassium thiocyanate
Aloe barbadensis
Saliveze
Carboxymethylcellulose
Calcium chloride
Methylparaben
 
GC Dry Mouth Gel
Cellulose gum/carrageenan
 
Ethylparaben
 
Saliva Orthana
Pig gastric mucin
Potassium fluoride
Benzoate
EDTA
Biotene
Xanthan gum/glycerine
Cetylpyridinium chloride
Benzoate, methylparaben
 
Glandosane
Sodium carboxymethylcellulose
Calcium chloride
Sodium chloride
 
As noted in Table 11.2 some artificial salivas also contain bioactives – components extracted from natural sources (animals or plants) that are added to replicate some of the bacteriostatic or antibacterial effects of natural saliva. The benefits of these added bioactives are largely unproven or at least difficult to distinguish from placebo effects [11]. However the addition of bioactives certainly warrants further attention and is likely to be the area in which greatest innovation of artificial salivas occurs. For example, non-salivary proteins could be added to improve the lubricating properties of saliva [16]. Indeed the inclusion of supercharged polypeptides [29] has already shown beneficial effects although their safety in humans has yet to be proven. The addition of calcium and fluoride should be a regular inclusion in artificial salivas to aid in the protection of teeth. Several chapters have already detailed the deleterious effects of a lack of saliva on tooth integrity. Since saliva is already naturally high in calcium, the addition of this ion would seem obvious; however, maintaining its solubility for long periods may be a problem for manufacturers. Likewise the addition of fluoride often requires an acidic medium to maintain its solubility. Usually an acidic saliva would not be recommended because it may lead to the accelerated dissolution of teeth. However as shown in Table 11.3, if there is any saliva present in the mouth – which will be true for most patients – the acidic pH of the artificial salivas will quickly be neutralised by saliva’s buffering system (bicarbonate, carbonic anhydrase and proteins). Hence the benefits of including calcium and fluoride probably outweigh the potential danger from the acidic pH, for most patients.

Table 11.3

The pH of artificial salivas and when mixed with whole mouth saliva (single subject)
pH
WMS
1:14
1:6
1:1
Artificial saliva
Saliveze
6.7
6.7
6.7
7.0
7.0
Saliva Orthana
6.7
6.6
6.6
6.6
6.5
Biotene
6.7
6.8
6.6
6.6
5.9
BioXtra
6.7
6.9
6.8
7.4
7.5
Even at high dilutions such as 1:14, saliva effectively neutralises acidic artificial salivas

Physical Properties of Artificial and Natural Salivas

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Nov 26, 2015 | Posted by in General Dentistry | Comments Off on Artificial Salivas: Why Are They Not More Useful?
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