Xerostomia, the subjective sensation of oral dryness, is a common yet frequently underrecognized condition with multifactorial etiology and substantial consequences for oral and systemic health. Salivary gland hypofunction underlies many, but not all, cases and may result from medication use, head and neck radiotherapy, autoimmune disease, systemic illnesses, or age-related and hormonal changes. Persistent xerostomia impairs mastication, swallowing, speech, taste, and sleep, and predisposes to dental caries, periodontal disease, oral infections, nutritional compromise, and diminished quality of life. Despite its high prevalence, especially among older adults and individuals receiving complex pharmacotherapy or oncologic treatments, diagnostic approaches and management strategies remain heterogeneous across clinical settings. This review synthesizes current knowledge on the structure and function of the salivary glands, the pathophysiology and clinical manifestations of xerostomia, and contemporary diagnostic and therapeutic approaches. Conventional management relies on a combination of patient education, modification of contributory medications where feasible, topical lubricants and saliva substitutes, topical fluoride and remineralizing agents, and systemic sialagogues in selected patients, supplemented by preventive and radioprotective strategies in oncology practice. However, these interventions are predominantly palliative and often provide incomplete or transient relief. Rapid advances in salivary gland biology, regenerative medicine, and materials science have generated a new generation of therapies aimed at preserving or restoring gland function. Investigational approaches include stem and progenitor cell-based therapies, gene transfer to residual gland tissue, biomimetic scaffolds and organoid technologies, and nanotechnology-enabled interventions such as targeted nanoparticle drug delivery and engineered nanozyme-based immunomodulation. By integrating foundational concepts with cutting-edge translational data, this review provides a framework for mechanism-based evaluation and management of xerostomia and highlights key priorities for future research.

Keywords: Xerostomia, Salivary Gland Hypofunction, Regenerative Medicine, Nanotechnology, Autoimmune Disease

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1. StatPearls. Xerostomia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
2. Wolff A, Joshi RK, Ekström J, Aframian D, Pedersen AM, Proctor G, et al. Xerostomia: a comprehensive review with a focus on mid-life health. Clin Exp Dent Res. 2022;8(5):993–1008.
3. Patil P, Kolekar S, Patil A. A review on xerostomia and its various management strategies. J Pharm Bioallied Sci. 2022;14(Suppl 1):S25–S34.
4. Tanasiewicz M, Hildebrandt T, Obersztyn I. Xerostomia of various etiologies: a review of the literature. Adv Clin Exp Med. 2016;25(1):199–206.
5. American Dental Association. Xerostomia (dry mouth). ADA Oral Health Topics; 2023.
6. Brink R, Ahlgren J, Ahlqvist E, Frithiof J, Hakeberg M, Wide U, et al. Xerostomia in primary care: a register-based study of prevalence and associated factors. Front Oral Health. 2025;2:1684568.
7. Thomson WM. Prevalence of xerostomia in population-based samples. J Dent Res. 2005;84(3):239–243.
8. Närhi TO, Meurman JH, Ainamo A. Xerostomia and hyposalivation: causes, consequences and treatment in the elderly. Drugs Aging. 1999;15(2):103–116.
9. Hegde MN, Hegde ND, Ashok A, Shetty S. Prevalence of xerostomia and its association with systemic diseases among subjects attending a dental college in Kerala. J Indian Acad Oral Med Radiol. 2021;33(3):252–258.
10. Napenas JJ, Brennan MT, Fox PC. Xerostomia: etiology, diagnosis, and treatment. Oral Maxillofac Surg Clin North Am. 2008;20(3):435–445.
11. Vissink A, Mitchell JB, Baum BJ, Limesand KH, Jensen SB, Fox PC, et al. Clinical management of salivary gland hypofunction and xerostomia after radiotherapy for head and neck cancer. Oral Oncol. 2010;46(6):464–475.
12. Chambers MS, Garden AS, Kies MS, Martin JW. Radiation-induced xerostomia in patients with head and neck cancer: pathogenesis, impact and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(1 Suppl):S45.e1–S45.e13.
13. Domingo E, Li H, Tsvetkov D, et al. Predicting radiotherapy-induced xerostomia in head and neck cancer patients by CT radiomics and dose–volume histogram. Cancers (Basel). 2022;14(21):5335.
14. Cooper JS, Fu K, Marks J, Silverman S. Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol Phys. 1995;31(5):1141–1164.
15. Jensen SB, Pedersen AM, Vissink A, Andersen E, Brown CG, Davies AN, et al. Salivary gland hypofunction and/or xerostomia induced by nonsurgical cancer therapies: ISOO/MASCC/ASCO guideline. J Clin Oncol. 2021;39(28):3090–3110.
16. Hafsah S, Syam S, et al. Association of xerostomia and polypharmacy: a case-control study. Eur Geriatr Med. 2025;16(1):45–53.
17. Baijens LW, Clavé P, Cras P, Ekberg O, Forster A, Kolb GF, et al. Where dysphagia begins: polypharmacy and xerostomia. Dysphagia. 2019;34(4):501–507.
18. Katagiri A, Okuda M, Otsuka R, et al. Relationship between polypharmacy, xerostomia, gustatory sensitivity, and swallowing complaints in the elderly: a multidisciplinary approach. J Textbook Geriatr Sci. 2020;5(3):145–153.
19. Fox RI. Sjögren’s syndrome. Lancet. 2005;366(9482):321–331.
20. Pringle S, van Os R, Coppes RP. From salivary gland stem cells to regenerative therapy. Oral Dis. 2023;29(5):1805–1818.
21. StatPearls. Sjögren syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
22. Kapourani A, et al. Xerostomia: etiology, diagnosis, prevalence, and treatment—a review. J Oral Med. 2023;9(1):B18–B27.
23. Ferreira JN, Hasan MM, Ghinassi B. Three-dimensional bioprinting nanotechnologies towards clinical application of stem cells and their secretome in salivary gland regeneration. J Tissue Eng Regen Med. 2017;11(10):3246–3261.
24. Ferreira JN, Hasan MM, Ghinassi B. Three-dimensional bioprinting nanotechnologies towards clinical application of stem cells and their secretome in salivary gland regeneration. Biomed Res Int. 2016;2016:7564689.
25. Park HJ, Kim JY, Lee J, et al. Organoid-based modeling and regenerative strategies for salivary gland disorders. Korean J Physiol Pharmacol. 2025;29(1):1–17.
26. Klangprapan S, et al. Bioprinting salivary gland models and their regenerative applications. Cell Death Discov. 2024;10:229.
27. Soria J, Peralta S, López-López J, Jané-Salas E. Nanoparticles and human saliva: a step towards drug delivery systems for dental and craniofacial biomaterials. Int J Nanomedicine. 2019;14:5957–5972.
28. de Lima R, de Oliveira JL, Campos EVR, Fraceto LF. The effect of saliva on the fate of nanoparticles. Eur Cell Mater. 2017;33:242–252.
29. Liu Y, Zhang X, Wang J, Li Z, Chen Y, Zhao Y, et al. Engineered nanozyme immunomodulator for xerostomia treatment. Nano Today. 2025;55:102003.
30. Wang J, Li Y, Zhou T, et al. Nanozymes in oral medicine: from catalytic design to advanced dental therapies. Small. 2025;21(32):e202507226.
31. Zhang R, Wu T, Li F, et al. Nanozymes: a promising solution for dental antibacterial applications. RSC Adv. 2024;14(45):29761–29781.
32. Naha PC, Liu Y, Hsu JC, Chng CK, et al. Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm control. Nat Commun. 2023;14:6213.
33. Wang Y, Liu B, Ma L, et al. The potential use of nanozymes as antibacterial agents in oral diseases. Front Bioeng Biotechnol. 2024;12:1380974.
34. Zhang Y, Wang H, Lu H, et al. Nanozyme: new horizons for responsive biomedical applications. Front Chem. 2019;7:399.
35. Javalkar T, Patil A, Naik SM. Enzyme-mimicking nanomaterials for diagnostics and therapeutics: an overview of nanozymes. Int J Pharm Pharm Res. 2025;14(1):1–20.
36. Yang B, Chen Y, Shi J. New horizons for the therapeutic application of nanozymes in inflammatory diseases. Front Pharmacol. 2025;16:1544399.
37. Fan H, Yan G, Zhao Z, Hu X, Zhang W, Liu H, et al. Nanozyme-mediated catalytic nanotherapy for inflammatory disease and cancer. Theranostics. 2019;9(10):3062–3073.
38. Li Q, Guo Z, Zhang S, et al. Regenerative cerium oxide nanozymes alleviate oxidative stress for tissue repair. Regen Biomater. 2022;9(3):rbac070.
39. Klymenko M, et al. Nanoceria alleviate oxidative and nitrosative stress in experimental models. Fiziol Zh. 2018;64(2):3–11.
40. Kim J, Park H, Lee J, et al. Biosafe cerium oxide nanozymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress. NPJ Regen Med. 2024;9:15.
41. Xu J, Li W, Chen Q, et al. Orally administered cerium oxide nanozyme for computed tomography imaging and therapeutic ROS scavenging. Small. 2023;19(4):e2204761.
42. Chen Q, Xu Y, Song M, et al. The regulatory mechanisms of cerium oxide nanoparticles in redox biology. Front Pharmacol. 2024;15:1312345.
43. Ariga K, et al. Designs, applications, and future perspectives of nanozymes in biomedicine. Eur Cell Mater. 2025;52:105–135.
44. Nikolopoulou A, et al. Nanotechnology applications in oral pathology: a scoping review. Diagnostics (Basel). 2025;15(3):xxx–xxx.
45. Loretz B, D’Amico A, Ehmann F, et al. Regulatory pathways and guidelines for nanotechnology-enabled health products: a comparative review of EU and US frameworks. Front Med (Lausanne). 2025;12:1544393.
46. European Medicines Agency. Nanotechnology-based medicinal products for human use: EU horizon scanning report. EMA; 2020. EMA/409956/2019.
47. European Medicines Agency. Multidisciplinary: nanomedicines—scientific guidelines [Internet]. EMA; 2016. Available from: https://www.ema.europa.eu
48. US Food and Drug Administration. Drug products, including biological products, that contain nanomaterials: guidance for industry. FDA; 2024.
49. US Food and Drug Administration. FDA’s approach to regulation of nanotechnology products. FDA; 2018.
50. Wei H, Wang E. Nanozymes: classification, catalytic mechanisms, activity regulation and applications. Chem Rev. 2019;119(1):18–114.

Xerostomia, the subjective sensation of oral dryness, is a common yet frequently underrecognized condition with multifactorial etiology and substantial consequences for oral and systemic health. Salivary gland hypofunction underlies many, but not all, cases and may result from medication use, head and neck radiotherapy, autoimmune disease, systemic illnesses, or age-related and hormonal changes. Persistent xerostomia impairs mastication, swallowing, speech, taste, and sleep, and predisposes to dental caries, periodontal disease, oral infections, nutritional compromise, and diminished quality of life. Despite its high prevalence, especially among older adults and individuals receiving complex pharmacotherapy or oncologic treatments, diagnostic approaches and management strategies remain heterogeneous across clinical settings. This review synthesizes current knowledge on the structure and function of the salivary glands, the pathophysiology and clinical manifestations of xerostomia, and contemporary diagnostic and therapeutic approaches. Conventional management relies on a combination of patient education, modification of contributory medications where feasible, topical lubricants and saliva substitutes, topical fluoride and remineralizing agents, and systemic sialagogues in selected patients, supplemented by preventive and radioprotective strategies in oncology practice. However, these interventions are predominantly palliative and often provide incomplete or transient relief. Rapid advances in salivary gland biology, regenerative medicine, and materials science have generated a new generation of therapies aimed at preserving or restoring gland function. Investigational approaches include stem and progenitor cell-based therapies, gene transfer to residual gland tissue, biomimetic scaffolds and organoid technologies, and nanotechnology-enabled interventions such as targeted nanoparticle drug delivery and engineered nanozyme-based immunomodulation. By integrating foundational concepts with cutting-edge translational data, this review provides a framework for mechanism-based evaluation and management of xerostomia and highlights key priorities for future research.

Keywords: Xerostomia, Salivary Gland Hypofunction, Regenerative Medicine, Nanotechnology, Autoimmune Disease

🔒 This is a subscription article

Full text is available to subscribers and institutional members. Please choose an option below to access it.

1. StatPearls. Xerostomia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
2. Wolff A, Joshi RK, Ekström J, Aframian D, Pedersen AM, Proctor G, et al. Xerostomia: a comprehensive review with a focus on mid-life health. Clin Exp Dent Res. 2022;8(5):993–1008.
3. Patil P, Kolekar S, Patil A. A review on xerostomia and its various management strategies. J Pharm Bioallied Sci. 2022;14(Suppl 1):S25–S34.
4. Tanasiewicz M, Hildebrandt T, Obersztyn I. Xerostomia of various etiologies: a review of the literature. Adv Clin Exp Med. 2016;25(1):199–206.
5. American Dental Association. Xerostomia (dry mouth). ADA Oral Health Topics; 2023.
6. Brink R, Ahlgren J, Ahlqvist E, Frithiof J, Hakeberg M, Wide U, et al. Xerostomia in primary care: a register-based study of prevalence and associated factors. Front Oral Health. 2025;2:1684568.
7. Thomson WM. Prevalence of xerostomia in population-based samples. J Dent Res. 2005;84(3):239–243.
8. Närhi TO, Meurman JH, Ainamo A. Xerostomia and hyposalivation: causes, consequences and treatment in the elderly. Drugs Aging. 1999;15(2):103–116.
9. Hegde MN, Hegde ND, Ashok A, Shetty S. Prevalence of xerostomia and its association with systemic diseases among subjects attending a dental college in Kerala. J Indian Acad Oral Med Radiol. 2021;33(3):252–258.
10. Napenas JJ, Brennan MT, Fox PC. Xerostomia: etiology, diagnosis, and treatment. Oral Maxillofac Surg Clin North Am. 2008;20(3):435–445.
11. Vissink A, Mitchell JB, Baum BJ, Limesand KH, Jensen SB, Fox PC, et al. Clinical management of salivary gland hypofunction and xerostomia after radiotherapy for head and neck cancer. Oral Oncol. 2010;46(6):464–475.
12. Chambers MS, Garden AS, Kies MS, Martin JW. Radiation-induced xerostomia in patients with head and neck cancer: pathogenesis, impact and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(1 Suppl):S45.e1–S45.e13.
13. Domingo E, Li H, Tsvetkov D, et al. Predicting radiotherapy-induced xerostomia in head and neck cancer patients by CT radiomics and dose–volume histogram. Cancers (Basel). 2022;14(21):5335.
14. Cooper JS, Fu K, Marks J, Silverman S. Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol Phys. 1995;31(5):1141–1164.
15. Jensen SB, Pedersen AM, Vissink A, Andersen E, Brown CG, Davies AN, et al. Salivary gland hypofunction and/or xerostomia induced by nonsurgical cancer therapies: ISOO/MASCC/ASCO guideline. J Clin Oncol. 2021;39(28):3090–3110.
16. Hafsah S, Syam S, et al. Association of xerostomia and polypharmacy: a case-control study. Eur Geriatr Med. 2025;16(1):45–53.
17. Baijens LW, Clavé P, Cras P, Ekberg O, Forster A, Kolb GF, et al. Where dysphagia begins: polypharmacy and xerostomia. Dysphagia. 2019;34(4):501–507.
18. Katagiri A, Okuda M, Otsuka R, et al. Relationship between polypharmacy, xerostomia, gustatory sensitivity, and swallowing complaints in the elderly: a multidisciplinary approach. J Textbook Geriatr Sci. 2020;5(3):145–153.
19. Fox RI. Sjögren’s syndrome. Lancet. 2005;366(9482):321–331.
20. Pringle S, van Os R, Coppes RP. From salivary gland stem cells to regenerative therapy. Oral Dis. 2023;29(5):1805–1818.
21. StatPearls. Sjögren syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
22. Kapourani A, et al. Xerostomia: etiology, diagnosis, prevalence, and treatment—a review. J Oral Med. 2023;9(1):B18–B27.
23. Ferreira JN, Hasan MM, Ghinassi B. Three-dimensional bioprinting nanotechnologies towards clinical application of stem cells and their secretome in salivary gland regeneration. J Tissue Eng Regen Med. 2017;11(10):3246–3261.
24. Ferreira JN, Hasan MM, Ghinassi B. Three-dimensional bioprinting nanotechnologies towards clinical application of stem cells and their secretome in salivary gland regeneration. Biomed Res Int. 2016;2016:7564689.
25. Park HJ, Kim JY, Lee J, et al. Organoid-based modeling and regenerative strategies for salivary gland disorders. Korean J Physiol Pharmacol. 2025;29(1):1–17.
26. Klangprapan S, et al. Bioprinting salivary gland models and their regenerative applications. Cell Death Discov. 2024;10:229.
27. Soria J, Peralta S, López-López J, Jané-Salas E. Nanoparticles and human saliva: a step towards drug delivery systems for dental and craniofacial biomaterials. Int J Nanomedicine. 2019;14:5957–5972.
28. de Lima R, de Oliveira JL, Campos EVR, Fraceto LF. The effect of saliva on the fate of nanoparticles. Eur Cell Mater. 2017;33:242–252.
29. Liu Y, Zhang X, Wang J, Li Z, Chen Y, Zhao Y, et al. Engineered nanozyme immunomodulator for xerostomia treatment. Nano Today. 2025;55:102003.
30. Wang J, Li Y, Zhou T, et al. Nanozymes in oral medicine: from catalytic design to advanced dental therapies. Small. 2025;21(32):e202507226.
31. Zhang R, Wu T, Li F, et al. Nanozymes: a promising solution for dental antibacterial applications. RSC Adv. 2024;14(45):29761–29781.
32. Naha PC, Liu Y, Hsu JC, Chng CK, et al. Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm control. Nat Commun. 2023;14:6213.
33. Wang Y, Liu B, Ma L, et al. The potential use of nanozymes as antibacterial agents in oral diseases. Front Bioeng Biotechnol. 2024;12:1380974.
34. Zhang Y, Wang H, Lu H, et al. Nanozyme: new horizons for responsive biomedical applications. Front Chem. 2019;7:399.
35. Javalkar T, Patil A, Naik SM. Enzyme-mimicking nanomaterials for diagnostics and therapeutics: an overview of nanozymes. Int J Pharm Pharm Res. 2025;14(1):1–20.
36. Yang B, Chen Y, Shi J. New horizons for the therapeutic application of nanozymes in inflammatory diseases. Front Pharmacol. 2025;16:1544399.
37. Fan H, Yan G, Zhao Z, Hu X, Zhang W, Liu H, et al. Nanozyme-mediated catalytic nanotherapy for inflammatory disease and cancer. Theranostics. 2019;9(10):3062–3073.
38. Li Q, Guo Z, Zhang S, et al. Regenerative cerium oxide nanozymes alleviate oxidative stress for tissue repair. Regen Biomater. 2022;9(3):rbac070.
39. Klymenko M, et al. Nanoceria alleviate oxidative and nitrosative stress in experimental models. Fiziol Zh. 2018;64(2):3–11.
40. Kim J, Park H, Lee J, et al. Biosafe cerium oxide nanozymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress. NPJ Regen Med. 2024;9:15.
41. Xu J, Li W, Chen Q, et al. Orally administered cerium oxide nanozyme for computed tomography imaging and therapeutic ROS scavenging. Small. 2023;19(4):e2204761.
42. Chen Q, Xu Y, Song M, et al. The regulatory mechanisms of cerium oxide nanoparticles in redox biology. Front Pharmacol. 2024;15:1312345.
43. Ariga K, et al. Designs, applications, and future perspectives of nanozymes in biomedicine. Eur Cell Mater. 2025;52:105–135.
44. Nikolopoulou A, et al. Nanotechnology applications in oral pathology: a scoping review. Diagnostics (Basel). 2025;15(3):xxx–xxx.
45. Loretz B, D’Amico A, Ehmann F, et al. Regulatory pathways and guidelines for nanotechnology-enabled health products: a comparative review of EU and US frameworks. Front Med (Lausanne). 2025;12:1544393.
46. European Medicines Agency. Nanotechnology-based medicinal products for human use: EU horizon scanning report. EMA; 2020. EMA/409956/2019.
47. European Medicines Agency. Multidisciplinary: nanomedicines—scientific guidelines [Internet]. EMA; 2016. Available from: https://www.ema.europa.eu
48. US Food and Drug Administration. Drug products, including biological products, that contain nanomaterials: guidance for industry. FDA; 2024.
49. US Food and Drug Administration. FDA’s approach to regulation of nanotechnology products. FDA; 2018.
50. Wei H, Wang E. Nanozymes: classification, catalytic mechanisms, activity regulation and applications. Chem Rev. 2019;119(1):18–114.