Radiotherapy is a widely used treatment modality for head and neck cancers but often associated with several complications, such as salivary gland hypofunction which causes reduction in salivary flow. This reduction can lead to xerostomia (dry mouth), enamel demineralization, and various oral health issues that significantly affect a patient’s quality of life. To overcome these challenges, artificial saliva in the form of oral care products such as mouthwashes and gels has been developed in research conducted at the Bauru School of Dentistry at the University of São Paulo (FOB-USP) in Brazil.
This research is currently laboratory based (in vitro) and the formulation is not yet commercially available. Clinical trials in human patients are still pending to confirm safety and effectiveness before market use.
According to the study, Flavio Henrique-Silva, Department of Genetics and Evolution, Federal University of Sao Carlos, Sao Carlos, Sao Paulo, Brazil, stated,
“We’ve developed a process in which CANECPI-5 binds directly to tooth enamel, helping to make teeth more resistant to the action of acids produced by bacteria.”
The study was conducted during Natara Dias Gomes da Silva’s doctoral studies at FOB-USP. She collaborated with researchers from the Federal University of São Carlos (UFSCar), also in Brazil; the University of California in San Francisco, in the United States; and Yonsei University College of Dentistry, in South Korea.
The work is part of the Thematic Project “Modulation of acquired pellicle to control dental mineral loss: unveiling mechanisms to make therapies possible”, which is coordinated by Professor Marilia Afonso Rabelo Buzalaf from FOB-USP.
The artificial salivary formulation has been developed by incorporating a special type of protein known as CaneCPI-5, which is a recombinant cystatin derived from sugarcane. This protein helps protect tooth enamel from demineralization. Demineralization is the process in which teeth lose minerals such as calcium and phosphate. This makes them more susceptible to cavities caused by acids from the stomach, alcoholic beverages, and other demineralizing agents.
Binding with hydroxyapatite crystals in the enamel due to its strong affinity for hydroxyapatite. This inhibits enamel erosion.
Modifying the basal layer of the acquired enamel pellicle, which is a thin organic layer on the surface of the teeth. This improves resistance to acids.
The data from the research study shows that the artificial saliva with CaneCPI -5 ,Fluoride and Xylitol as combined agents produced significant results in reducing bacterial activity and tooth demineralization than artificial saliva with CaneCPI-5 used as a single agent.
According to the study 1, Marilia Afonso Rabelo Buzalaf, Department of Biological Sciences, Bauru School of Dentistry, University of Sao Paulo, Bauru, Sao Paulo, Brazil, stated,
“This is the first product that uses the concept of acquired pellicle [a thin protective layer that quickly forms on the tooth surface] to treat xerostomia, which is the sensation of a dry mouth caused by a lack of saliva. We use substances that will reformulate the composition of the proteins that bind to the teeth”
Used to treat Xerostomia (dry mouth caused by lack of saliva) after Radiotherapy in Head and Neck cancer patients.
Helps in reduction of cavities by preventing demineralization.
The study also found partial antimicrobial and anticaries activity in vitro.
Buzalaf added: “Artificial saliva improves the sensation of dry mouth and sores. This helps with discomfort and also combats bacteria. In some cases, the use of this type of product is only for a short time. In others, it’s permanent, because many individuals lose the ability to produce saliva.”
Currently available saliva substitutes mainly contain carboxymethylcellulose, glycerin, or mucin-based lubricants that provide temporary moisture but do not actively protect enamel or modify the acquired pellicle. 2
In contrast, the CaneCPI-5 enriched formulation offers a bioactive approach by binding to enamel and enhancing resistance to acid attacks, which may provide superior protection against tooth decay compared to conventional dry mouth treatments.
The patent for the CANECPI-5 protein was filed a few years ago. Researchers currently aim to collaborate with companies interested in the technology, so that artificial saliva containing this protein can be manufactured and made available for use.
Researchers are also planning to continue the study further to understand how CaneCPI-5 interacts with other substances such as statherin, a protein found in saliva and Vitamin E.
“Another aspect of the Thematic Project is to associate CANECPI-5 with vitamin E because this vitamin acts as a carrier, bringing the protein into contact with the tooth. We imagine that this could facilitate the application of the product directly by the patient at home,” says the researcher.
What is artificial saliva?
Artificial saliva is a laboratory-formulated oral product designed to mimic natural saliva. It is commonly used as a dry mouth treatment for people with salivary gland damage due to radiotherapy, medications, or autoimmune conditions.
Who needs artificial saliva?
Patients undergoing head and neck cancer treatment, individuals with Sjögren’s syndrome, and people experiencing medication-induced dry mouth may benefit from saliva substitutes.
Is this new formulation of CaneCPI-5 enriched artificial saliva available in the market?
No. This CaneCPI-5 enriched artificial saliva is currently in the laboratory research stage. Human clinical trials are still pending before commercial availability.
How is it different from regular saliva substitutes?
Unlike conventional products that only provide lubrication, this formulation actively binds to tooth enamel and helps prevent demineralization and cavities.
1. Natara Dias Gomes Da Silva , Paulo Sérgio da Silva Santos , Flavio Henrique-Silva , Ana Carolina Magalhaes , Marcos Roberto Chiaratti , Elbert de Josselin de Jong , Pamela K DenBesten , Marília Afonso Rabelo Buzalaf.“A novel artificial saliva enriched with CaneCPI-5 for irradiated head and neck cancer (HNC) patients: in vitro antimicrobial and anticaries effect”.Journal of Dentistry,volume 163,December 2025.Accessed January 9,2026.https://www.sciencedirect.com/science/article/abs/pii/S0300571225006220.
2. Furness, S., Worthington, H. V., Bryan, G., Birchenough, S., and McMillan, R. “Interventions for the Management of Dry Mouth: Non-Pharmacological Interventions.” Cochrane Database of Systematic Reviews (2013). https://doi.org/10.1002/14651858.CD009603.pub2
