Laffleur Flavia, Schmelzle Franziska, Ganner Ariane, Vanicek Stefan
Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80/82, 6020, Innsbruck, Austria.
Institute for Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
AAPS PharmSciTech. 2017 Aug;18(6):2102-2109. doi: 10.1208/s12249-016-0676-y. Epub 2016 Dec 27.
This study aimed to develop a mucoadhesive polymeric excipient comprising curcumin for buccal delivery. Curcumin encompasses broad range of benefits such as antioxidant, anti-inflammatory, and chemotherapeutic activity. Hyaluronic acid (HA) as polymeric excipient was modified by immobilization of thiol bearing ligands. L-Cysteine (SH) ethyl ester was covalently attached via amide bond formation between cysteine and the carboxylic moiety of hyaluronic acid. Succeeded synthesis was proved by H-NMR and IR spectra. The obtained thiolated polymer hyaluronic acid ethyl ester (HA-SH) was evaluated in terms of stability, safety, mucoadhesiveness, drug release, and permeation-enhancing properties. HA-SH showed 2.75-fold higher swelling capacity over time in comparison to unmodified polymer. Furthermore, mucoadhesion increased 3.4-fold in case of HA-SH and drug release was increased 1.6-fold versus HA control, respectively. Curcumin-loaded HA-SH exhibits a 4.4-fold higher permeation compared with respective HA. Taking these outcomes in consideration, novel curcumin-loaded excipient, namely thiolated hyaluronic acid ethyl ester appears as promising tool for pharyngeal diseases.
本研究旨在开发一种含姜黄素的用于口腔给药的黏膜黏附性聚合物辅料。姜黄素具有广泛的益处，如抗氧化、抗炎和化疗活性。作为聚合物辅料的透明质酸（HA）通过固定含硫醇配体进行了改性。L-半胱氨酸（SH）乙酯通过半胱氨酸与透明质酸羧基部分之间形成酰胺键而共价连接。通过H-NMR和IR光谱证明了合成成功。对所得的硫醇化聚合物透明质酸乙酯（HA-SH）的稳定性、安全性、黏膜黏附性、药物释放和渗透增强性能进行了评估。与未改性的聚合物相比，HA-SH随时间的溶胀能力高出2.75倍。此外，HA-SH的黏膜黏附性增加了3.4倍，与HA对照相比，药物释放增加了1.6倍。载有姜黄素的HA-SH与相应的HA相比，渗透高出4.4倍。考虑到这些结果，新型载姜黄素辅料，即硫醇化透明质酸乙酯似乎是治疗咽部疾病的有前途的工具。
