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    Next Generation Salivary Lubrication Enhancer Derived from Recombinant Supercharged Polypeptides for Xerostomia

    Year: 2020

    Journal: ACS Appl. Mater. Interfaces, Volume 12, AUG 5, page 34524–34535

    Authors: Wan, Hongping; Ma, Chao; Vinke, Jeroen; Vissink, Arjan; Herrmann, Andreas; Sharma, Prashant K.

    Keywords: biolubrication; recombinant supercharged polypeptides; ex vivo oral lubrication system; salivary substitutes; saliva; mucins; dry mouth; Sjogren's syndrome; protein adsorption

    Insufficient retention of water in adsorbed salivary conditioning films (SCFs) because of altered saliva secretion can lead to oral dryness (xerostomia). Patients with xerostomia sometimes are given artificial saliva, which often lacks efficacy because of the presence of exogenous molecules with limited lubrication properties. Recombinant supercharged polypeptides (SUPs) improve salivary lubrication by enhancing the functionality of endogenously available salivary proteins, which is in stark contrast to administration of exogenous lubrication enhancers. This novel approach is based on establishing a layered architecture enabled by electrostatic bond formation to stabilize and produce robust SCFs in vitro. Here, we first determined the optimal molecular weight of SUPs to achieve the best lubrication performance employing biophysical and in vitro friction measurements. Next, in an ex vivo tongue-enamel friction system, stimulated whole saliva from patients with Sjogren syndrome was tested to transfer this strategy to a preclinical situation. Out of a library of genetically engineered cationic polypeptides, the variant SUP K108cys that contains 108 positive charges and two cysteine residues at each terminus was identified as the best SUP to restore oral lubrication. Employing this SUP, the duration of lubrication (Relief Period) for SCFs from healthy and patient saliva was significantly extended. For patient saliva, the lubrication duration was increased from 3.8 to 21 min with SUP K108cys treatment. Investigation of the tribochemical mechanism revealed that lubrication enhancement is because of the electrostatic stabilization of SCFs and mucin recruitment, which is accompanied by strong water fixation and reduced water evaporation.
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