Budai-Szűcs Mária, Horvát Gabriella, Gyarmati Benjámin, Szilágyi Barnabás Áron, Szilágyi András, Berkó Szilvia, Ambrus Rita, Szabó-Révész Piroska, Sandri Giuseppina, Bonferoni Maria Cristina, Caramella Carla, Csányi Erzsébet
Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
Soft Matters Group, Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
Eur J Pharm Biopharm. 2017 Apr;113:178-187. doi: 10.1016/j.ejpb.2016.12.026. Epub 2017 Jan 11.
Thiolated polymers are a promising new group of excipients, but their stability against atmospheric oxidation has not been investigated in detail, and only a few efforts have been made to improve their stability. The oxidation of the thiol groups in solutions of thiolated polymers may result in a decrease of mucoadhesion and unpredictable in situ gelation. The aims of our work were to study the stability of aqueous solutions of thiolated polymers and the effects of stabilizing agents. We investigated thiolated poly(aspartic acid) polymers stabilized with dithiothreitol, glutathione or acetylcysteine. The effects of these antioxidants on the gel structure, mucoadhesion and drug release were determined by means of scanning electron microscopy, swelling, rheology, adhesion and drug release tests. It was concluded that the stability of polymer solutions containing antioxidants is sufficient for one day. Polymers stabilized with dithiotreitol demonstrated fast swelling and drug release, but weaker mucoadhesion as compared with the other samples. Polymers stabilized with glutathione displayed the weakest cohesive properties, resulting in fast and uncontrolled drug release and moderate mucoadhesion. Acetylcysteine-stabilized polymers exhibited an optimum cross-linked structure, with free thiol groups ensuring polymer-mucin interactions, resulting in the best mucoadhesive properties.
硫醇化聚合物是一类很有前景的新型辅料，但它们对大气氧化的稳定性尚未得到详细研究，而且在改善其稳定性方面所做的努力也很少。硫醇化聚合物溶液中硫醇基团的氧化可能会导致粘膜粘附性下降和不可预测的原位凝胶化。我们工作的目的是研究硫醇化聚合物水溶液的稳定性以及稳定剂的作用。我们研究了用二硫苏糖醇、谷胱甘肽或乙酰半胱氨酸稳定的硫醇化聚天冬氨酸聚合物。通过扫描电子显微镜、溶胀、流变学、粘附和药物释放测试来确定这些抗氧化剂对凝胶结构、粘膜粘附性和药物释放的影响。得出的结论是，含有抗氧化剂的聚合物溶液的稳定性足以维持一天。用二硫苏糖醇稳定的聚合物表现出快速溶胀和药物释放，但与其他样品相比粘膜粘附性较弱。用谷胱甘肽稳定的聚合物表现出最弱的内聚性，导致药物快速且不受控制地释放以及中等的粘膜粘附性。乙酰半胱氨酸稳定的聚合物表现出最佳的交联结构，游离的硫醇基团确保了聚合物与粘蛋白的相互作用，从而产生了最佳的粘膜粘附性能。
