Entirely S-protected silicone oil as second generation mucoadhesive agent

Aim: Design of entirely S-protected silicone oils providing superior mucoadhesion and potential mucoprotection. Methods: 2-Mercaptonicotinic acid (MNA) and its dimer (MNA-MNA) were coupled to amino-modified silicone oil. Thiolated and S-protected silicone oil were assessed regarding rheological mucus interaction, mucoadhesion and potential mucoprotection. Results: For thiolated silicone-MNA and S-protected silicone-MNA-MNA almost quantitative coupling efficiencies could be achieved with total MNA amounts of 193 +/- 15 mu mol/g and 398 +/- 44 mu mol/g, respectively. Especially for S-protected silicone oil a firm mucus interaction was determined with an up to 28-fold increase in viscosity in comparison to non-thiolated control. Both silicone thiomers showed enhanced mucoadhesive features with remaining amounts of 18.1 +/- 2.5% for silicone-MNA and 44.9 +/- 4.8% for silicone-MNA-MNA after 8 h on intestinal mucosa, whereas non-thiolated control was washed away within 4 h. In view of a potential mucoprotective effect, methylene blue release was below 15% for silicone-MNA-MNA upon 8 h of incubation on intestinal and conjunctival mucosa in contrast to 100% leakage for the control. Conclusion: Entirely S-protected silicone oil as second generation mucoadhesive can be ascribed with outstanding mucoadhesion and mucoprotective potential, which renders it a promising tool for mucosal targeting and inflammation treatment modalities. (C) 2016 Elsevier Ltd. All rights reserved.