Artificial saliva

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Artificial saliva for dry mouth in a mouthwash form Artificial saliva.jpg
Artificial saliva for dry mouth in a mouthwash form

Artificial saliva or salivary substitutes refer to a synthetically produced liquid that mimics the natural secretion of saliva. It is designed as a symptomatic relief for xerostomia, a condition characterised by dryness in the mouth and is available over-the-counter. The efficacy of artificial saliva in a systematic review of clinical trials indicates that all evaluated products reduce xerostomia symptoms, but the comparative effectiveness remains unclear due to study inconsistencies and potential biases. Side effects are uncommon, but users should take precautions against possible side effects such as allergic reactions.

Contents

Artificial saliva is mainly composed of bioactive compounds, which substitute for natural saliva's biological functions, such as facilitating antimicrobial activity, digestion and lubrication of oral tissues. Additional components such as buffering and flavouring agents are added to increase the stability of formulations and user acceptance, respectively. These formulations are available in various forms and have varied chemical-physical properties.

Current research on artificial saliva focuses on expanding its functionality by incorporating synthetic molecules similar to their biological counterparts in natural saliva. The study includes efforts to enhance native salivary proteins and synthesise novel molecules using various chemical and genetic engineering techniques.

Clinical applications

Artificial saliva is primarily used to relieve symptoms of xerostomia, known as dry mouth and hyposalivation, which is a condition that results in reduced saliva production. Various factors, including medication use, cancer therapy, and certain diseases, such as diabetes, stroke or Sjögren syndrome, can cause xerostomia. [1] Artificial saliva supplements any pre-existing saliva in individuals with xerostomia, and its primary function is to restore moisture in the oral cavity. [2] Artificial saliva is available over-the-counter and comes in various formulations, including gels, mouth rinses and sprays. [3]

Artificial saliva also contributes to oral health maintenance by promoting enamel defence against acidic erosion. In individuals with a high intake of soft drinks or a high vomiting frequency and a decrease in saliva flow, artificial saliva can help improve the clearance time of acids and reduce the chance of dental erosion.

Efficacy

The assessment of artificial saliva's efficacy reveals a consensus that all evaluated products contribute to reducing xerostomia symptoms in a systematic review of clinical trials. The review indicated that herbal products are better than artificial saliva in alleviating symptoms of radiation-induced xerostomia, while oral spray presentation and saliva substitutes containing 3% citric acid provide longer-lasting relief for drug-induced xerostomia. The selection and combination of saliva substitutes should be tailored to the individual's needs, preferences and oral health status. Despite the variety of products tested, a definitive judgment on their comparative effectiveness is challenging due to the heterogeneity of the studies in terms of the products, sites and durations involved and many studies exhibit a high risk of bias. [4]

Side effects

Side effects of artificial saliva are relatively uncommon but still exist with varying severity. Minor side effects might not necessitate medical attention. However, in certain instances, users may experience symptoms indicative of an allergic reaction, such as rash, hives, itching, and swelling in the mouth, face, lips, tongue or throat and should consult a doctor. [5] [6] Common side effects include:

Warnings

Individuals with fructose intolerance should be aware that certain artificial saliva products contain fructose and should be avoided. Users adhering to a sodium-restricted diet must exercise caution when selecting an artificial saliva product, as some, including Caphosol, may contain considerable amounts of sodium. [7]

Composition

Artificial saliva comprises an array of bioactive compounds designed to mimic the natural functions of human saliva to alleviate symptoms of dry mouth by aiding in speaking and swallowing, and it provides general comfort by simulating the sticky consistency of natural saliva. The composition typically includes cellulose derivatives, buffering and flavouring agents as core components, ensuring the product's efficacy and palatability. [8]

Cellulose derivatives

Cellulose derivatives are rheological modifiers, which are compounds responsible for the viscosity and texture of artificial saliva, enabling it to adhere to oral tissues and provide a protective and lubricating film. [9] The viscosity of cellulose derivatives is greater than that of natural human saliva. [10] Cellulose derivatives include:

Mucin

Mucin is a glycoprotein prevalent in natural saliva, and lab-made mucin can closely replicate the characteristics of natural saliva by forming a protective and lubricative film on oral surfaces. [11] Mucin has an elevated adsorption capacity compared to carboxymethyl cellulose-based formulations, which improves lubrication. Clinical trials have indicated a preference among users for saliva substitutes containing mucin compared to those formulated with carboxymethyl cellulose. [12]

Glycerol

Glycerol is a colourless and odourless lipid and can coat oral surfaces. It aids in humidifying and lubricating the oral cavity, easing discomfort associated with dry mouth conditions. [13] Glycerol is a Newtonian fluid with a higher viscosity than natural human saliva. [10]

Enzymes

Enzymes in artificial saliva mimic natural saliva's antimicrobial and digestive functions by contributing to the breakdown of food particles and inhibiting the growth of harmful bacteria, which improves oral health and assists in the digestive process. [10] Enzymes include:

Minerals

Minerals contribute to dental integrity and serve a protective function in the oral environment. The minerals aid in the remineralisation process, which repairs tooth enamel that might have been demineralised due to various oral conditions or acidic environments. For example, fluoride forms fluorapatite, a compound more resistant to decay than the original hydroxyapatite of the tooth enamel. [14] Minerals include:

Buffering agents

Buffering agents in artificial saliva maintain the pH levels, ensuring the oral environment remains within the optimal range for enamel protection and microbial balance. A stable pH prevents tooth decay and maintains oral health. These buffering agents neutralise acidic substances in the oral cavity, safeguarding tooth enamel and soft tissues from acid-related damage. Buffering agents include:

Flavouring agents

Flavouring agents enhance the taste and acceptability of artificial saliva. These agents can mask any unpleasant flavours inherent in the other components and make the user's experience of using artificial saliva more pleasant. Flavouring agents encourage the user's compliance with the treatment regimen, mainly when long-term use is necessary. [4] Flavouring agents include:

Types

Artificial saliva is available in different types and varies in chemical-physical properties, including viscosity, pH, buffering capacity, superficial tension, density and spinnbarkeit. [15] Types of artificial saliva include:

Research

Research on artificial saliva focuses on replicating the biological components of natural saliva to substitute and enhance essential functions such as aiding digestion, performing antimicrobial action and protecting tissue layers. [16] Approaches include enhancing or mimicking salivary proteins in natural saliva.

Enhancing salivary proteins

Salivary proteins such as histatin, statherin and mucin, which possess antimicrobial, lubrication and biomineralisation properties, are targets of enhancement in artificial saliva research as they are significant in maintaining oral health. [10]

Genetic engineering and recombinant DNA techniques produce recombinant salivary proteins for enhanced biological functions. [10] Identification of recombinant histatin and statherin strains is more prevalent as they are smaller and simpler in structure. Therefore, a range of histatin and statherin variants with duplication of active protein domain or removal of phosphorylated serine that enhances antimicrobial activities and enamel biomineralisation were developed and produced. [16]

Recombinant mucins were less widely produced previously due to challenges imposed by the repetitive nature of their DNA sequences, which often results in highly truncated, suboptimal protein production. [10] Substantial research was devoted to developing custom gene synthesis methods to overcome these challenges. The methods were guided by codon scrambling algorithms to reduce repetition in DNA sequences while conserving important information for recombinant protein synthesis. [17]

The downstream genetic expression system of recombinant salivary proteins is also a key area of research, as it affects glycosylation patterns that contribute to their stability and lubrication properties. Efficient modification of glycosylation genes in host cells through genetic engineering techniques like CRISPR/Cas9 to produce salivary proteins with specific glycan phenotypes, which enhance the stability of artificial saliva. [17]

Synthesising novel molecules

Synthesising novel molecules that mimic natural salivary proteins' complete or partial structure is a key aspect of artificial saliva research. [11]

Fully synthesised molecules from a chemical engineering approach include mirror-image mucins and thio-mucins, produced from monomers incorporated with enantiomer amino acids and modified glycan linkages, respectively. These structural analogs have tunable biodegradation rates while maintaining their ability to bind with salivary proteins, thus improving artificial saliva's stability and lubrication properties. [18]

Another class of novel molecules developed from a genetic engineering approach to mimic salivary proteins are recombinant supercharged polypeptides (SUPs). They are produced from the construction of new DNA sequences that express SUPs consisting of repetitive units encoding for glycine (G), valine (V), proline (P), and lysine (K) amino acids. This polypeptide class has increased interaction with the layering of salivary conditioning films (SCFs) coating oral tissues, which helps improve oral lubrication. [19]

Novel molecules developed to mimic partial structures of salivary proteins include chemically modified O-glycans, using methods such as direct oxidation and metabolic glycoengineering. The modified O-glycans facilitate mucin conjugation with other molecules in the oral cavity for enhanced physical properties and bioactivity. [17]

Related Research Articles

Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into the blood stream. Digestion is a form of catabolism that is often divided into two processes based on how food is broken down: mechanical and chemical digestion. The term mechanical digestion refers to the physical breakdown of large pieces of food into smaller pieces which can subsequently be accessed by digestive enzymes. Mechanical digestion takes place in the mouth through mastication and in the small intestine through segmentation contractions. In chemical digestion, enzymes break down food into the small compounds that the body can use.

<span class="mw-page-title-main">Saliva</span> Bodily fluid secreted by salivary glands

Saliva is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells, enzymes, and antimicrobial agents.

Dysgeusia, also known as parageusia, is a distortion of the sense of taste. Dysgeusia is also often associated with ageusia, which is the complete lack of taste, and hypogeusia, which is a decrease in taste sensitivity. An alteration in taste or smell may be a secondary process in various disease states, or it may be the primary symptom. The distortion in the sense of taste is the only symptom, and diagnosis is usually complicated since the sense of taste is tied together with other sensory systems. Common causes of dysgeusia include chemotherapy, asthma treatment with albuterol, and zinc deficiency. Liver disease, hypothyroidism, and rarely, certain types of seizures can also lead to dysgeusia. Different drugs can also be responsible for altering taste and resulting in dysgeusia. Due to the variety of causes of dysgeusia, there are many possible treatments that are effective in alleviating or terminating the symptoms. These include artificial saliva, pilocarpine, zinc supplementation, alterations in drug therapy, and alpha lipoic acid.

<span class="mw-page-title-main">Salivary gland</span> Exocrine glands that produce saliva through a system of ducts

The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands, as well as hundreds of minor salivary glands. Salivary glands can be classified as serous, mucous, or seromucous (mixed).

<span class="mw-page-title-main">Uremia</span> Type of kidney disease, urea in the blood

Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which would be normally excreted in the urine. Uremic syndrome can be defined as the terminal clinical manifestation of kidney failure. It is the signs, symptoms and results from laboratory tests which result from inadequate excretory, regulatory, and endocrine function of the kidneys. Both uremia and uremic syndrome have been used interchangeably to denote a very high plasma urea concentration that is the result of renal failure. The former denotation will be used for the rest of the article.

<span class="mw-page-title-main">Xerostomia</span> Medical condition

Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause.

<span class="mw-page-title-main">Mucin</span> Glycoprotein

Mucins are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. They often take an inhibitory role. Some mucins are associated with controlling mineralization, including nacre formation in mollusks, calcification in echinoderms and bone formation in vertebrates. They bind to pathogens as part of the immune system. Overexpression of the mucin proteins, especially MUC1, is associated with many types of cancer.

<span class="mw-page-title-main">Dental erosion</span> Medical condition

Acid erosion is a type of tooth wear. It is defined as the irreversible loss of tooth structure due to chemical dissolution by acids not of bacterial origin. Dental erosion is the most common chronic condition of children ages 5–17, although it is only relatively recently that it has been recognised as a dental health problem. There is widespread ignorance of the damaging effects of acid erosion; this is particularly the case with erosion due to consumption of fruit juices because they tend to be seen as healthy. Acid erosion begins initially in the enamel, causing it to become thin, and can progress into dentin, giving the tooth a dull yellow appearance and leading to dentin hypersensitivity.

<span class="mw-page-title-main">Meth mouth</span> Tooth decay caused by methamphetamine use

Meth mouth is a colloquial term used to describe severe tooth decay and tooth loss, as well as tooth fracture, acid erosion, and other oral problems that are often symptomatic to extended use of the drug methamphetamine. The condition is thought to be caused by a combination of side effects of the drug and lifestyle factors, which may be present in long-term users. However, the legitimacy of meth mouth as a unique condition has been questioned because of the similar effects of some other drugs on teeth. Images of diseased mouths are often used in anti-drug campaigns.

Dental plaque is a biofilm of microorganisms that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found between the teeth, on the front of teeth, behind teeth, on chewing surfaces, along the gumline (supragingival), or below the gumline cervical margins (subgingival). Dental plaque is also known as microbial plaque, oral biofilm, dental biofilm, dental plaque biofilm or bacterial plaque biofilm. Bacterial plaque is one of the major causes for dental decay and gum disease.

A sialogogue is a substance, especially a medication, that increases the flow rate of saliva. The definition focuses on substances that promote production or secretion of saliva rather than any food that is mouthwatering.

<span class="mw-page-title-main">STATH</span> Protein-coding gene in humans

Statherin is a protein in humans that is encoded by the STATH gene. It prevents the precipitation of calcium phosphate in saliva, maintaining a high calcium level in saliva available for remineralisation of tooth enamel and high phosphate levels for buffering.

<span class="mw-page-title-main">Histatin 1</span> Protein-coding gene in the species Homo sapiens

Histatin-1 is a protein that in humans is encoded by the HTN1 gene.

<span class="mw-page-title-main">Remineralisation of teeth</span>

Tooth remineralization is the natural repair process for non-cavitated tooth lesions, in which calcium, phosphate and sometimes fluoride ions are deposited into crystal voids in demineralised enamel. Remineralization can contribute towards restoring strength and function within tooth structure.

Oral ecology is the microbial ecology of the microorganisms found in mouths. Oral ecology, like all forms of ecology, involves the study of the living things found in oral cavities as well as their interactions with each other and with their environment. Oral ecology is frequently investigated from the perspective of oral disease prevention, often focusing on conditions such as dental caries, candidiasis ("thrush"), gingivitis, periodontal disease, and others. However, many of the interactions between the microbiota and oral environment protect from disease and support a healthy oral cavity. Interactions between microbes and their environment can result in the stabilization or destabilization of the oral microbiome, with destabilization believed to result in disease states. Destabilization of the microbiome can be influenced by several factors, including diet changes, drugs or immune system disorders.

Biotene is an over-the-counter dental hygiene product currently marketed GSK plc. It comes in a number of forms, including toothpaste, mouthwash and gel.

Proline-rich proteins (PRPs) is a class of intrinsically unstructured proteins (IUP) containing several repeats of a short proline-rich sequence.

<span class="mw-page-title-main">Lactoperoxidase</span> Mammalian protein found in Homo sapiens

Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary and other mucosal glands including the lungs, bronchii and nose that functions as a natural and the first line of defense against bacteria and viruses. Lactoperoxidase is a member of the heme peroxidase family of enzymes. In humans, lactoperoxidase is encoded by the LPO gene.

<span class="mw-page-title-main">Salivary gland disease</span> Medical condition

Salivary gland diseases (SGDs) are multiple and varied in cause. There are three paired major salivary glands in humans: the parotid glands, the submandibular glands, and the sublingual glands. There are also about 800–1,000 minor salivary glands in the mucosa of the mouth. The parotid glands are in front of the ears, one on side, and secrete mostly serous saliva, via the parotid ducts, into the mouth, usually opening roughly opposite the second upper molars. The submandibular gland is medial to the angle of the mandible, and it drains its mixture of serous and mucous saliva via the submandibular duct into the mouth, usually opening in a punctum in the floor of mouth. The sublingual gland is below the tongue, on the floor of the mouth; it drains its mostly mucous saliva into the mouth via about 8–20 ducts, which open along the plica sublingualis, a fold of tissue under the tongue.

<span class="mw-page-title-main">Human digestive system</span> Digestive system in humans

The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion. Digestion involves the breakdown of food into smaller and smaller components, until they can be absorbed and assimilated into the body. The process of digestion has three stages: the cephalic phase, the gastric phase, and the intestinal phase.

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