International Journal of Molecular Sciences Review Artificial Saliva: Challenges and Future Perspectives for the Treatment of Xerostomia Dawid Łysik 1 , Katarzyna Niemirowicz-Laskowska 2, Robert Bucki 3 , Gra˙zynaTokajuk 4 and Joanna Mystkowska 1,* 1 Department of Materials Engineering and Production, Bialystok University of Technology, Wiejska 45C, 15-351 Bialystok, Poland 2 Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-295 Bialystok, Poland 3 Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland 4 Department of Integrated Dentistry, Medical University of Bialystok, M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland * Correspondence: [email protected]; Tel.: +48-571-443-083 Received: 23 May 2019; Accepted: 28 June 2019; Published: 29 June 2019 Abstract: The chronic sensation of a dry mouth is a disease condition called xerostomia and affects a large part of the population. Xerostomia is associated with decreased secretion, or more often, qualitative changes in saliva proteins and immunoglobulin concentrations that develop as a result of salivary gland dysfunction. Several reasons causing dry mouth were described, and usually, they include taking medications, diseases or radiotherapy. In some situations, when it is difficult to use salivary stimulants or salivary gland damage is irreversible, the only option might seem to be saliva substitutes. The paper presents the most important aspects considering saliva preparations. The rheological and lubricating properties and the reconstruction of the complex saliva structure has been the main purpose of research. The biological properties of saliva preparations were also widely discussed. As part of the work, the antimicrobial effect of three commercial saliva preparations was tested. Finally, inadequate antimicrobial properties against the strains isolated from the oral cavity were demonstrated. The development of salivary substitutes, in particular, the improvement of antimicrobial properties, can be achieved using nanotechnology, including drug delivery systems containing nanocarriers. Keywords: artificial saliva; xerostomia; rheology 1. Introduction Most people who have been upset, anxious or under stress have experienced a dry mouth. This is a subjective feeling of reduced secretion of saliva in the mouth, associated not only with its amount but rather regarding quantitative and qualitative changes in saliva composition. The feeling of dry and cracked lips, sticky and viscous saliva, altered taste and smell, difficulty talking, problems with chewing, tooth caries and their increased erosion, heartburn and reflux exacerbation, oesophagitis, burning tongue, festering and irritating mucous membrane infections are the consequences of salivary gland dysfunction [1]. Living with reduced saliva secretion is not only difficult but also leads to serious health problems such as xerostomia. In such situations, therapeutic methods for stimulation of saliva secretion are used. However, in some cases, salivary gland damage requires continuous use of saliva substitutes [2–4]. The main purpose of this review was an analysis of the most important aspects concerning saliva preparations due to its microbial, rheological and lubrication properties. Int. J. Mol. Sci. 2019, 20, 3199; doi:10.3390/ijms20133199 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2019, 20, 3199 2 of 17 Int. J. Mol. Sci. 2019, 20, x 2 of 17 2. Xerostomia:2. Xerostomia: Etiology Etiology of of Salivary Salivary Glands Glands Dysfunctions Dysfunctions TheThe chronic chronic sensation sensation of dryof dry mouth mouth leads leads to ato disease a disease entity entity called called xerostomia. xerostomia. The The number number of of undesirableundesirable factors factors aff affectingecting salivary salivary glands, glands, people people su ffsufferingering from from stress, stress, exposed exposed to to many many diseases, diseases, andand aging aging can can make make xerostomia xerostomia a globala global problem. problem. In In prospective prospective population population studies studies [5 ]([5]n (=n 2942,= 2942, adultsadults aged aged 20–59), 20–59), it wasit was shown shown that that regular regular xerostomia xerostomia symptoms symptoms concern concern about about 3.8%, 3.8%, while while irregular,irregular, 12.2% 12.2% of theof the population. population. In In studies studies of of older older people people [6 ]([6]n (=n 600,= 600, over over 70 70 years years of of age) age) in in Japan,Japan, the the hyposalivation hyposalivation problem problem was was observed observed in in 37.3% 37.3% of of patients patients (27.8% (27.8% in in men men and and 47.3% 47.3% in in women).women). In In other other studies, studies, Cardoso Cardoso et et al. al. [7 ][7] found foun thatd that 45.5% 45.5% of disease-freeof disease-free oropharyngeal oropharyngeal cancer cancer survivorssurvivors (n (=n 906)= 906) reported reported problems problems with with dry dry mouth. mouth.Rising Rising interestinterest inin xerostomiaxerostomia andand methods of ofits treatment,treatment, especiallyespecially usingusing artificialartificial saliva,saliva, is is currently currently observed. observed. This This is is clearly clearly visible visible in in the the bibliometricbibliometric data data (Figure (Figure1), according1), according to the to the Web Web of Science of Science database. database. The The term term “xerostomia” "xerostomia" inyears in years 2000–20182000–2018 was was found found in 3671in 3671 publications, publications, which which were were quoted quoted more more than than 70,000 70,000 times, times, while while the the term term “artificial"artificial saliva” saliva" related related to 2757to 2757 publications, publications, which which were were cited cited about about 37,000 37,000 times. times. (a) (b) FigureFigure 1. A1. number A number of articles of articles andcitations and citations regarding regarding the terms: the (aterms:) “xerostomia”, (a) “xerostomia”, (b) “artificial (b) “artificial saliva” accordingsaliva” toaccording the Web to of the Science Web database.of Science database. 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TheThe term term saliva, saliva, by default,by default, refers refers to the to the terms terms "whole "whole saliva" saliva" or "mixed or "mixed saliva", saliva", which which are used are used to describeto describe the combined the combined fluids presentfluids present in the oral in the cavity. oral Measurement cavity. Measurement of its quantity of its isquantity a good methodis a good to determinemethod to determine the degree the of drynessdegree of of dryness the mouth, of the while mouth, the while measurement the measurement of salivary of salivary secretion secretion from specificfrom salivaryspecific salivary gland allows gland determination allows determination of its individual of its individual efficiency efficiency [1]. [1]. SalivaSaliva can can be be classified classified as as resting resting (unstimulated) (unstimulated) and and stimulated. stimulated. 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HyposalivationmL per minute [1]. is observedHyposalivation when is restingobserved salivary when flow resting rate decreases salivary flow below rate 0.1 decreas mL peres minute below and0.1 mL stimulated per minute saliva and below stimulated 0.5–0.7 mLsaliva perbelow minute 0.5–0.7 [1,9,10 mL]. Theper salivaryminute [1,9,10].