Hauptstein Sabine, Bonengel Sonja, Rohrer Julia, Bernkop-Schnürch Andreas
Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Eur J Pharm Sci. 2014 Oct 15;63:132-9. doi: 10.1016/j.ejps.2014.07.002. Epub 2014 Jul 11.
The study was aimed to developed and investigate a novel polymer for intestinal drug delivery with improved mucoadhesive properties. Therefore Eudragit® L 100-55 (poly(methacrylic acid-co-ethyl acrylate)) was thiolated by covalent attachment of L-cysteine. The immobilized thiol groups were preactivated by disulfide bond formation with 2-mercaptonicotinic acid. Resulting derivative (Eu-S-MNA) was investigated in terms of mucoadhesion via three different methods: tensile studies, rotating cylinder studies and rheological synergism method, as well as water-uptake capacity and cytotoxicity. Different derivatives were obtained with increasing amount of bound L-cysteine (60, 140 and 266 μmol/g polymer) and degree of preactivation (33, 45 and 51 μmol/g polymer). Tensile studies revealed a 30.5-, 35.3- and 52.2-fold rise of total work of adhesion for the preactivated polymers compared to the unmodified Eudragit. The adhesion time on the rotating cylinder was prolonged up to 17-fold in case of thiolated polymer and up to 34-fold prolonged in case of the preactivated polymer. Rheological synergism revealed remarkable interaction of all investigated modified derivatives with mucus. Further, water-uptake studies showed an over 7h continuing weight gain for the modified polymers whereat disintegration took place for the unmodified polymer within the first hour. Cell viability studies revealed no impact of modification. Accordingly, the novel preactivated thiolated Eudragit-derivative seems to be a promising excipient for intestinal drug delivery.
该研究旨在开发和研究一种具有改善的粘膜粘附特性的新型用于肠道给药的聚合物。因此，通过L-半胱氨酸的共价连接对Eudragit® L 100-55（聚（甲基丙烯酸-co-丙烯酸乙酯））进行硫醇化。通过与2-巯基烟酸形成二硫键对固定的硫醇基团进行预活化。通过三种不同方法对所得衍生物（Eu-S-MNA）的粘膜粘附性进行了研究：拉伸研究、旋转圆筒研究和流变协同作用方法，以及吸水性和细胞毒性。随着结合的L-半胱氨酸量（60、140和266 μmol/g聚合物）和预活化程度（33、45和51 μmol/g聚合物）的增加，获得了不同的衍生物。拉伸研究表明，与未改性的Eudragit相比，预活化聚合物的总粘附功提高了30.5倍、35.3倍和52.2倍。硫醇化聚合物在旋转圆筒上的粘附时间延长了17倍，预活化聚合物延长了34倍。流变协同作用表明，所有研究的改性衍生物与粘液之间存在显著相互作用。此外，吸水性研究表明，改性聚合物的重量增加持续超过7小时，而未改性聚合物在第一小时内就发生了崩解。细胞活力研究表明改性没有影响。因此，新型预活化硫醇化Eudragit衍生物似乎是一种有前途的肠道给药辅料。
