Entirely S-Protected Thiolated Silicone: A Novel Hydrophobic Mucoadhesive and Skin Adhesive

The aim of this study was the synthesis and evaluation of an entirely S-protected thiolated silicone as novel hydrophobic mucoadhesive and skin adhesive. 2-[(2-Amino-2-carboxyethyl)disulfanyl]nicotinic acid was covalently attached to a poly(dimethylsiloxane)-graft-polyacrylate via amide bond formation. Adhesive properties were determined via the rotating cylinder method and tensile studies on porcine small intestinal mucosa besides on porcine abdominal skin. Rheological characteristics were evaluated on a cone-plate rheometer. The S-protected thiolated silicone exhibited 128 ± 18 μmol immobilized 2-mercaptonicotinic acid per gram of polymer and showed a 5.9-fold extended time of mucosal adhesion compared with the unmodified silicone on the rotating cylinder. With a 2.3-fold higher maximum detachment force and a 1.7-fold higher total work of adhesion tested on porcine small intestinal mucosa, the S-protected thiolated silicone is superior to the unmodified silicone. Furthermore, using porcine abdominal skin, a 2.4-fold higher maximum detachment force and a 4.4-fold higher total work of adhesion obtained for the S-protected thiolated silicone outlines the preferentially adhesion to skin. Triggered by N-acetyl-L-cysteine liberated thiol groups form interchain and intrachain disulfide bonds within the polymer (6.7% m/v) causing a 23.0-fold increase in dynamic viscosity (ƞ). In parallel, the elastic modulus (G') and the viscous modulus (G") increased 39.2-fold and 8.1-fold, respectively.