Saliva substitute from University of Leeds scientists offers major relief for dry mouth conditions

By Pooja Toshniwal PahariaNov 23 2023Reviewed by Danielle Ellis, B.Sc.

In a recent study published in Scientific Reports, researchers compared the in vitro lubrication performance of a patented microgel-based aqueous hydrogel lubricant formulation in its dairy and vegan formulation to that of various commercially available saliva substitutes, classified into "liquids," "viscous liquids," and "gels" based on shear rheology and extensional properties.

Xerostomia, or dry mouth, characterized by reduced saliva, produces oral friction, potentially leading to dental caries, periodontal disease, candidiasis, oral ulcers, and dysphagia. As a consequence, food intake is often lowered, leading to malnutrition with detrimental influences on nutritional status and quality of life.

Saliva alternatives are available; however, they often lack the biological surface adsorption-inducing 'border lubrication' required for these scenarios. In-vitro, a proprietary colloidal aqueous lubricant demonstrated improved lubricity equivalent to actual human saliva. Lubricant benchmarking could accelerate its clinical transition.

About the study

In the present study, researchers compared the in vitro oral lubrication performance of a new colloidal aqueous microgel-reinforced hydrogel-based formulation made with dairy or vegan proteins to commercially available products using rheological, tribological, and adsorption/desorption measurements on dry mouth surfaces.

Two aqueous lubricant formulations were created using lactoferrin and potato protein isolate, resulting in microgels of varying sizes. A vegan form of the aqueous lubricant was developed using varied pH, heat treatment, and homogenization settings. Dynamic light scattering experiments were performed to estimate microgel hydrodynamic diameters (dH). Human saliva was obtained from healthy volunteers and analyzed. Human saliva's rheological, lubricating, and adsorption characteristics were measured and utilized as controls for comparison.

The dairy lubricant comprised a thermally cross-linked lactoferrin protein-based microgel partly covered by a carrageenan hydrogel, whereas the vegan lubricant comprised xanthan gum hydrogels and potato protein-based microgels in a patchy network. Both the laboratory-prepared aqueous lubricant formulations were viscoelastic and sub-micron in size with minimal polydispersity. Lubricant shear resistance was evaluated and compared to commercially available salivary substitutes to assess their viscosity characteristics and categorize them based on their rheological properties.

The team performed tribology experiments to analyze the oral friction-reducing effects using a standard mini-traction machine with smooth hydrophobic elastomeric surfaces. They assessed lubrication behavior using a tribological setup with a steel plate-on-plate geometry (50 nm diameters) in the presence of more physiologically relevant surfaces. A QCM-D fitted with PDMS-coated sensors was used to assess the ability to adsorb onto a dry mouth-mimicking surface.

Based on the shear values, commercial salivary substitutes and the fabricated aqueous lubricants were classified as liquids with shear values <0.1 Pa s, viscous liquids with shear values between 0.1 and 1.0 Pa s, and gels with shear values >10 Pa s. The team assessed the capacity of the manufactured aqueous lubricants to minimize oral friction and preserve the oral cavity using dry mouth-mimicking surfaces and compared them to commercial salivary replacements. They evaluated extensibility using a single product for each shear category.

Results

The aqueous lubricant, which was more viscous than human saliva, remarkably reduced boundary friction in the in vitro xerostomic conditions to 41% to 99%, levels much higher than salivary alternatives formulated as sprays and thickened liquids. The enhanced lubricity was due to much lower desorption (seven percent) compared to the commercial salivary substitutes (23% to 58%) and increased shear viscosity permitting lubrication of fluid films, advantages over commercial brands.

The improved oral lubricity and retention capacities demonstrated by the aqueous lubricant for the in vitro biologically-simulated surfaces were due to optimized synergism between the high-viscosity polysaccharide hydrogel providing hydrodynamic lubrication and the effectively adsorbing, protein-based microgel yielding boundary lubrication. The results offered the first evidence of the capacity of the aqueous lubricant to outperform as a saliva substitute due to its high boundary lubrication and restricted desorption qualities.

The team assessed the sensory perception of manufactured lubricants using samples with varying surface hydrophobicity and contact forces. They found that whereas smooth and textured surfaces had identical surface hydrophobicity, contact forces and speeds varied, resulting in differential film thickness. Liquids exhibited comparable frictional curves to buffers, viscous liquids created lower friction coefficients, and gels offered lower friction coefficients in the border regime. Dairy and vegan substitutes decreased friction significantly between surfaces in contact.

Conclusion

Overall, the extensive benchmarking study findings showed that microgel-based aqueous lubricant formulations might be a potential therapy for dry mouth. The unique hydrogel composition decreases friction between dehydrated oral surfaces, which may help relieve discomfort. Dairy protein lubricates hydrophobic surfaces more efficiently than commercial saliva-replacing solutions, providing up to 99% more effective lubrication and 88% higher retention. Further sensory evaluations and clinical studies are required to confirm the effectiveness of these formulations.