RESUMEN
Xerostomia, the subjective sensation of 'dry mouth' affecting at least 1 in 10 adults, predominantly elders, increases life-threatening infections, adversely impacting nutritional status and quality of life. A patented, microgel-reinforced hydrogel-based aqueous lubricant, prepared using either dairy or plant-based proteins, has been demonstrated to offer substantially enhanced lubricity comparable to real human saliva in in vitro experiments. Herein, we present the benchmarking of in vitro lubrication performance of this aqueous lubricant, both in its dairy and vegan formulation 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 offers 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 might be 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). This comprehensive benchmarking study therefore paves the way for employing these microgel-based aqueous lubricant formulations as a novel topical platform for dry mouth therapy.
Asunto(s)
Microgeles , Xerostomía , Adulto , Humanos , Anciano , Saliva/química , Hidrogeles , Lubricantes/química , Benchmarking , Calidad de Vida , Saliva Artificial , Xerostomía/terapia , ExcipientesRESUMEN
HYPOTHESES: Bile salts (BS) are biosurfactants released into the small intestine, which play key and contrasting roles in lipid digestion: they adsorb at interfaces and promote the adsorption of digestive enzymes onto fat droplets, while they also remove lipolysis products from that interface, solubilising them into mixed micelles. Small architectural variations on their chemical structure, specifically their bile acid moiety, are hypothesised to underlie these conflicting functionalities, which should be reflected in different aggregation and solubilisation behaviour. EXPERIMENTS: The micellisation of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ by one hydroxyl group on the bile acid moiety, was assessed by pyrene fluorescence spectroscopy, and the morphology of aggregates formed in the absence and presence of fatty acids (FA) and monoacylglycerols (MAG) - typical lipolysis products - was resolved by small-angle X-ray/neutron scattering (SAXS, SANS) and molecular dynamics simulations. The solubilisation by BS of triacylglycerol-incorporating liposomes - mimicking ingested lipids - was studied by neutron reflectometry and SANS. FINDINGS: Our results demonstrate that BS micelles exhibit an ellipsoidal shape. NaTDC displays a lower critical micellar concentration and forms larger and more spherical aggregates than NaTC. Similar observations were made for BS micelles mixed with FA and MAG. Structural studies with liposomes show that the addition of BS induces their solubilisation into mixed micelles, with NaTDC displaying a higher solubilising capacity.
Asunto(s)
Ácidos y Sales Biliares , Micelas , Lipólisis , Dispersión del Ángulo Pequeño , Difracción de Rayos XRESUMEN
Methylcellulose (MC) has a demonstrated capacity to reduce fat absorption, hypothetically through bile salt (BS) activity inhibition. We investigated MC cholesterol-lowering mechanism, and compared the influence of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ slightly by their architecture and exhibit contrasting functions during lipolysis. BS/MC bulk interactions were investigated by rheology, and BS behaviour at the MC/water interface studied with surface pressure and ellipsometry measurements. In vitro lipolysis studies were performed to evaluate the effect of BS on MC-stabilised emulsion droplets microstructure, with confocal microscopy, and free fatty acids release, with the pH-stat method. Our results demonstrate that BS structure dictates their interactions with MC, which, in turn, impact lipolysis. Compared to NaTC, NaTDC alters MC viscoelasticity more significantly, which may correlate with its weaker ability to promote lipolysis, and desorbs from the interface at lower concentrations, which may explain its higher propensity to destabilise emulsions.
RESUMEN
HYPOTHESES: Understanding the mechanisms underlying lipolysis is crucial to address the ongoing obesity crisis and associated cardiometabolic disorders. Bile salts (BS), biosurfactants present in the small intestine, play key roles in lipid digestion and absorption. It is hypothesised that their contrasting functionalities - adsorption at oil/water interfaces and shuttling of lipolysis products away from these interfaces - are linked to their structural diversity. We investigate the interfacial films formed by two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), differing by the presence or absence of a hydroxyl group on their steroid skeleton. EXPERIMENTS: Their adsorption behaviour at the air/water interface and interaction with a phospholipid monolayer - used to mimic a fat droplet interface - were assessed by surface pressure measurements and ellipsometry, while interfacial morphologies were characterised in the lateral and perpendicular directions by Brewster angle microscopy, X-ray and neutron reflectometry, and molecular dynamics simulations. FINDINGS: Our results provide a comprehensive molecular-level understanding of the mechanisms governing BS interfacial behaviour. NaTC shows a higher affinity for the air/water and lipid/water interfaces, and may therefore favour enzyme adsorption, whereas NaTDC exhibits a higher propensity for desorption from these interfaces, and may thus more effectively displace hydrolysis products from the interface, through dynamic exchange.