Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52 c, Josef-Möller-Haus, 6020 Innsbruck, Austria.
AAPS PharmSciTech. 2010 Mar;11(1):174-80. doi: 10.1208/s12249-009-9370-7. Epub 2010 Jan 26.
The aim of this study was to modify pectin by covalent attachment of the water-insoluble ligand 4-aminothiophenol to its polymeric backbone. 4-Aminothiophenol is a ligand which is highly prone to oxidation. Therefore, this ligand allows oxidative cross-linking of pectin under mild oxidative conditions. Additionally, hydrophobization of pectin can be achieved by the mentioned modification which offers certain advantages over highly hydrophilic native pectins. 4-Aminothiophenol was covalently attached to pectin via amide bond formation between carboxylic moieties of pectin and the amino-group of 4-aminothiophenol. Two different pectin-4-aminothiophenol conjugates were synthesized and investigated regarding the amount of coupled ligand, rheological behavior under oxidative conditions, swelling behavior, and cytotoxic effects. Within this study, 557.3 +/- 49.0 and 158.8 +/- 23.1 micromol 4-aminothiophenol have been coupled per gram pectin. Within both conjugates, around 75% of the bound ligand appeared in its reduced form. Within rheological studies, a 500-fold increase in viscosity was achieved by addition of hydrogen peroxide as an oxidizing agent. Investigations on the swelling behavior revealed that this hydrophobic modification of pectin results in decelerated water uptake on the one hand and improved cohesive properties after oxidation of thiol groups to disulfide bonds on the other hand. Thereby, the maximum amount of water which can be uptaken by pectin matrices could be increased. According to these results, Pec-ATP conjugates could be valuable tools for several pharmaceutical applications due to the established method of gelation and the altered swelling and disintegration behavior.
本研究旨在通过共价键将不溶于水的配体 4-氨基苯硫酚连接到果胶的聚合物主链上来修饰果胶。4-氨基苯硫酚是一种极易氧化的配体。因此，该配体允许在温和的氧化条件下通过氧化交联果胶。此外，通过所述修饰可以实现果胶的疏水性化，这与高度亲水性的天然果胶相比具有某些优势。4-氨基苯硫酚通过果胶的羧酸基团与 4-氨基苯硫酚的氨基之间的酰胺键形成共价连接到果胶上。合成了两种不同的果胶-4-氨基苯硫酚缀合物，并研究了其偶联配体的量、氧化条件下的流变行为、溶胀行为和细胞毒性作用。在本研究中，每克果胶偶联了 557.3 ± 49.0 和 158.8 ± 23.1 μmol 的 4-氨基苯硫酚。在这两种缀合物中，约 75%的结合配体以其还原形式存在。在流变学研究中，通过添加过氧化氢作为氧化剂，可使粘度增加 500 倍。溶胀行为的研究表明，一方面，果胶的疏水性修饰导致水吸收速度减慢，另一方面，巯基氧化为二硫键后提高了果胶的内聚性能。因此，可以增加果胶基质中可以吸收的最大水量。根据这些结果，由于建立的凝胶化方法和改变的溶胀和崩解行为，Pec-ATP 缀合物可以成为几种药物应用的有价值工具。
