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

ACS Applied Materials & Interfaces, vol. 12, pp. 34524–34535

Abstract

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 Sjögren 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.

Authors 5

1. Hongping Wan

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   University Medical Center Groningen, Department of Biomedical Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands

2. Chao Ma

   University of Groningen · Zernike Institute for Advanced Materials

   Affiliation as printed

   Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands

3. Jeroen G. Vinke

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   University Medical Center Groningen, Department of Biomedical Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands

4. Arjan Vissink

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   University Medical Center Groningen, Department of Oral and Maxillofacial Surgery, University of Groningen, 9713 GZ Groningen, The Netherlands

5. Prashant Kumar Sharma corresponding

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   University Medical Center Groningen, Department of Biomedical Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands