Research Center for Nanosciences and Nanotechnology, Bandung Institute of Technology, Ganesha 10, Bandung, 40132, Indonesia.
School of Pharmacy, Research Center for Nanosciences and Nanotechnology, Bandung Institute of Technology, Ganesha 10, Bandung, 40132, Indonesia.
AAPS PharmSciTech. 2019 Feb 13;20(3):112. doi: 10.1208/s12249-018-1205-y.
We have successfully conjugated mesalamine (5-aminosalicylic acid, 5-ASA) with xylan, a biopolymer isolated from pineapple stem waste, to form xylan-5-ASA conjugate. The biopolymer was used to provide colon-targeting properties for 5-ASA, a golden standard anti-inflammatory agent commonly used for ulcerative colitis treatment. A series of data from FTIR spectroscopy, UV-Vis spectrophotometry, and HPLC confirmed the xylan-5-ASA conjugate formation. To ensure successful colon targeting properties, in vitro and in vivo drug release studies after oral administration of xylan-5-ASA conjugate to Wistar rats were performed. Xylan-5-ASA conjugate was able to retain 5-ASA release in the upper gastrointestinal tract fluid simulation but rapidly released 5-ASA in the rat colon fluid simulation. In vivo release profile shows a very low peak plasma concentration, reached at 6 h after xylan-5-ASA conjugate administration. The delayed release and the lower bioavailability of 5-ASA from xylan-5-ASA conjugate administration compared to free 5-ASA administration confirmed the successful local colon delivery of 5-ASA using xylan-5-ASA conjugate. The administration of xylan-5-ASA conjugate also exhibited greater efficacy in recovering 2,4,6-trinitrobenzene sulfonic acid-induced colon ulcer compared to free 5-ASA administration. Taken together, xylan isolated from pineapple stem waste is promising to obtain colon targeting property for 5-ASA.
我们成功地将美沙拉嗪（5-氨基水杨酸，5-ASA）与木聚糖偶联，木聚糖是一种从菠萝茎废弃物中分离得到的生物聚合物。该生物聚合物用于为 5-ASA 提供结肠靶向特性，5-ASA 是一种常用于溃疡性结肠炎治疗的标准抗炎药物。一系列来自傅里叶变换红外光谱、紫外可见分光光度法和高效液相色谱法的数据证实了木聚糖-5-ASA 偶联物的形成。为了确保成功的结肠靶向特性，在 Wistar 大鼠口服木聚糖-5-ASA 偶联物后进行了体外和体内药物释放研究。木聚糖-5-ASA 偶联物能够在模拟上消化道液中保留 5-ASA 的释放，但在大鼠结肠液模拟中迅速释放 5-ASA。体内释放曲线显示，木聚糖-5-ASA 偶联物给药后 6 小时达到非常低的血浆峰浓度。与游离 5-ASA 给药相比，木聚糖-5-ASA 偶联物给药后 5-ASA 的释放延迟和生物利用度降低，证实了使用木聚糖-5-ASA 偶联物成功实现了 5-ASA 的局部结肠递药。与游离 5-ASA 给药相比，木聚糖-5-ASA 偶联物给药还表现出在恢复 2,4,6-三硝基苯磺酸诱导的结肠溃疡方面的更高疗效。总之，从菠萝茎废弃物中分离得到的木聚糖有望获得 5-ASA 的结肠靶向性。
