ERC PoC Project AquaLub

AquaLub (A new high-performance aqueous lubricant formulation for soft bio-contact surfaces) is a European Research Council Proof of Concept (ERC PoC) funded research project for 1.5 years (2020-22) with a value of €150,000. In this ERC PoC project, we will translate an innovative aqueous lubricant technology, developed in the context of the ERC project LubSat, towards commercial applications. The technological focus is on an electrostatically-driven macromolecular self-assembly of biopolymeric structures. Commercial aqueous lubricants market is significantly growing ($22 billion by 2025) with broad range of personal care and institutional care applications to enhance hydration and alleviate dryness-related pathologies of oral, ocular, vaginal, rectal and/or urethral tissues.

In this context, hydrophilic polymers are the standard materials that provide sub-optimal lubrication properties significantly impairing the quality of life. Taking inspiration from highly sophisticated bio-lubricant saliva, engineered by nature, we propose a novel technology exploiting the self-assembly of proteinaceous and non-proteinaceous biopolymeric structures to design a porous mesh that acts as a nano-reservoir of water to provide the fluid film lubrication whilst the hydrophobic attachment of the proteinaceous structures to the surface provide the boundary lubrication. These dual-benefits have not been achieved by any commercial solutions to date. This technology allows for substantial improvements on enhancing lubrication and sustaining hydration of biological soft surfaces, over existing commercially-available approaches. In this project, we will validate the techno-commercial feasibility of the aqueous lubricant formulation in various formats and generate connections with key industrial players. Key activities in the proposed project will ensure demonstration of the up-scaling feasibility and validation of performance, market research and filing IP, which will allow us to build strategic alliances with selected industrial partners, explore licensing of the IP to these partners, and build a robust business case to take forward the commercialization of this technology.

New research article titled on 'Benchmarking of a microgel-reinforced hydrogel-based aqueous lubricant against commercial saliva substitutes' published in Scientific Reports

Dry mouth affecting 1 in 10 adults with rates as high as 30% in older adults and 80% in institutionalised older adults is one of the significant burdens on overall healthcare worldwide today. led by In this work published in Scientific Reports https://doi.org/10.1038/s41598-023-46108-w titled "Benchmarking of a microgel-reinforced hydrogel-based aqueous lubricant against commercial saliva substitutes", A patented, microgel-reinforced hydrogel-based aqueous lubricant, was prepared using either dairy or plant-based proteins as a novel salivary substitute (see the Figure top) and demonstrated to offer substantially enhanced lubricity comparable to the sole components forming these composite aqueous lubricants in in vitro experiments. The of in vitro lubrication performance of this aqueous lubricants, both in its dairy and vegan formulation was benchmarked in this study against a range of widely available and employed commercial saliva substitutes, latter classified based on their shear rheology into “liquids”, “viscous liquids” and “gels”, and also had varying extensional properties. Strikingly, the fabricated dairy-based aqueous lubricant offered up to 41–99% more effective boundary lubrication against liquids and viscous liquids, irrespective of topography of the tested dry mouth-mimicking tribological surfaces. Such high lubricity of the fabricated lubricants was attributed to their limited real-time desorption (7%) from a dry-mouth mimicking hydrophobic surface unlike the tested commercial products including gels (23–58% desorption). The inefficient lubrication properties and short relief period displayed by currently marketed products are attributed to their inability to stick efficiently onto biological surfaces (human tongue and palate), in turn thought to be due to their lack of mucoadhesive molecules—whose importance in oral lubrication has been largely neglected until now. In contrast, the biocompatible aqueous lubricant provides both high moisturising capacity (long lasting hydration, thanks to the water-encapsulating biopolymeric hydrogel) and strong ability to stay on biological surfaces following ingestion (boundary lubrication, thanks to the efficiently adsorbing proteinaceous microgel). This robust proof-of-concept in vitro work is a first step towards shedding light on the high potential of microgel-based aqueous lubricants to work as a saliva substitute for dry mouth sufferers, and will certainly act as a springboard for future sensory evaluation and follow-up phase I clinical trials to confirm the subjective perception of moistness and real-world efficacy with dry mouth sufferers, respectively.

New review article titled on 'Dry mouth diagnosis and saliva substitutes—A review from a textural perspective' published in Journal of Texture Studies

A new review has been published in Journal of Texture Studies https://doi.org/10.1111/jtxs.12575 covering a comprehensive summary of various diagnostic tools for assessment of dry mouth conditions and examined the salivary substitutes providing textural properties emulating those of real human saliva for treatment of dry mouth condition. Examination of both the current practices as well as emerging possibilities in dry mouth diagnosis and treatment, including a patent scan for saliva substitutes is included. The review shows that in terms of diagnosis, salivary flow rate test and questionnaire have been commonly used in clinical setting with subjective questionnaires being the most common approach. However, to date, there has been little attention on assessing the alternation in biochemical composition and mechanical properties of saliva in dry mouth patients. Biochemical composition, rheological, adsorption and tribological properties are important feature of saliva contributing to its unique functions, which are widely studied by researchers. It is thus crucial to employ these mechanical measurements on saliva from dry mouth patients in order to rationally tailor the kind of saliva substitute needed for their relief. For instance, if the dry mouth patient has residual saliva which contains high levels of lubricating salivary proteins but lacking in the hydrodynamic properties, then a thickening agent might be an ideal solution. However, if the salivary quality of the dry mouth patient suffers from lack of adsorption and boundary lubrication properties that are measured using quartz crystal microbalance with dissipation monitoring (QCM‐D) and tribological analyses, respectively, more effective saliva substitute that can act as boundary lubricants should be approached. Such personalized design of saliva substitutes would likely provide optimum treatment outcome of xerostomia. Another important challenge is to find a correlation between objectively measured salivary properties (e.g., lubrication, adsorption, mucin content) and subjective assessment of dry mouth. The lack of correlations hinder clinical adoption of these techniques for routine evaluation of dry mouth conditions by dental practitioners.

For treatment, eight composition agents have been identified within the commercial saliva substitute products as shown in the figure below, while four of them were directly relating to relief of oral dryness including lubricating, thickening, adhesive and moisturizing agents have been identified. Materials such as polysaccharides, mucin and cellulose‐based derivatives have been commonly discussed materials in literature. In addition to these commonly used component agents, innovative technologies such as self‐assembly, emulsion, liposomes, and microgels are emerging as novel saliva substitutes, indicating a trend of employing food‐related materials such as yam, okra etc. In summary, further pre‐clinical characterization of innovative technologies are needed and clear benefits of these technologies in terms of mucoadhesion, lubrication ad relief period over existing saliva substitutes need to be established before such materials can be used for clinical trials.

New Results on 'Synergistic microgel-reinforced hydrogels as high-performance lubricants' published in ACS Macro Letters

Xerostomia, clinically defined as the subjective complaint of “dry mouth” has an estimated prevalence of approximately 20% in the general population. The prevalence increases to 46% in older people aged >75 years, attributable in part to co-morbidity conditions and polymedication/ polypharmacy. Other causes, include, but not limited to, autoimmune exocrinopathy (e.g. primary Sjögren's syndrome (pSS)), radiotherapy, sarcoidosis, HIV, hepatitis C and poorly-controlled diabetes mellitus. Xerostomia has a detrimental impact on quality of life affecting the most essential activities such as speaking and eating, with dysphagia inhibiting easy entrance of nutrients and increases the risks of malnutrition. Furthermore, it increases the risk of dental complications such as, caries, periodontal disease, candidiasis, and oral ulceration. Xerostomia represents an enormous and growing health burden resulting from an increase in the global aging population and highlights the need for more effective topical dry mouth therapies.

In this paper published in ACS Macro Letters, Volume 9, Pages 1726-1731 (https://doi.org/10.1021/acsmacrolett.0c00689), a nonlipid biolubricant with strikingly low friction coefficients is fabricated (which is already patented) by reinforcing a fluid-like hydrogel composed of biopolymeric nanofibrils with proteinaceous microgels is proposed as a high performance salivary substitute, which synergistically provides superlubricity on elastomeric surfaces in comparison to any of the sole components. This two-component lubricant composed of positively-charged lactoferrin microgels (LFM) and negatively-charged κ-carrageenan hydrogels (κCH) as shown in the Figure below

is capable of exceeding the high lubricating performance of real human saliva in tribo-tests using both smooth and textured surfaces (see the lubrication data in the Figure below),

latter mimicking the human tongue’s wettability, topography, and compliance. The favorable electrostatic attraction between mutually oppositely charged microgels and the hydrogel reinforces the mechanical properties of the hydrogel, allowing friction reduction by combining the benefits of both viscous and hydration lubrication. The superlubricity of these microgel-reinforced hydrogels offers a unique prospect for the fabrication of biocompatible aqueous lubricants for dry-mouth therapy, ongoing work is dedicated to commerciliaze this patented technology with the help of NEXUS at University of Leeds, UK.