Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
J Pharm Sci. 2019 Sep;108(9):2887-2894. doi: 10.1016/j.xphs.2019.04.003. Epub 2019 Apr 8.
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.
本研究旨在合成和评价一种完全 S 保护的巯基化硅酮，作为新型疏水性黏附剂和皮肤黏附剂。通过酰胺键形成，将 2-[(2-氨基-2-羧乙基)二硫基]烟酸共价连接到聚（二甲基硅氧烷）-接枝-聚丙烯酸上。通过旋转圆筒法和拉伸研究，测定了对猪小肠黏膜的黏附性能，以及对猪腹部皮肤的黏附性能。在锥板流变仪上评估了流变特性。S 保护的巯基化硅酮每克聚合物固定了 128±18μmol 的 2-巯基烟酸，在旋转圆筒上与未改性的硅酮相比，黏膜黏附时间延长了 5.9 倍。在猪小肠黏膜上，最大分离力提高了 2.3 倍，黏附总功提高了 1.7 倍，S 保护的巯基化硅酮优于未改性的硅酮。此外，在使用猪腹部皮肤时，S 保护的巯基化硅酮的最大分离力提高了 2.4 倍，黏附总功提高了 4.4 倍，表明其优先黏附于皮肤。被释放的 N-乙酰-L-半胱氨酸触发的巯基在聚合物内形成链间和链内二硫键（6.7%m/v），导致动态黏度（η）增加 23.0 倍。同时，弹性模量（G'）和粘性模量（G"）分别增加了 39.2 倍和 8.1 倍。
