Tozaki Hideyuki, Odoriba Tomokazu, Okada Naoki, Fujita Takuya, Terabe Akira, Suzuki Tsutomu, Okabe Susumu, Muranishi Shozo, Yamamoto Akira
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
J Control Release. 2002 Jul 18;82(1):51-61. doi: 10.1016/s0168-3659(02)00084-6.
The objective of this study was to achieve the colon-specific delivery of an anti-ulcerative colitis drug using chitosan capsules and to accelerate healing of 2,4,6-trinitrobenzene sulfonic acid sodium salt (TNBS)-induced colitis in rats. 5-Aminosalicylic acid (5-ASA) was used as a model of an anti-inflammatory drug. The gastrointestinal transit of chitosan capsules was determined by counting the number of capsules in the gastrointestinal lumen by celiotomy at certain times after their oral administration to rats. The chitosan capsules reached the large intestine 3.5 h after oral administration in rats. We studied the release of 5-ASA from chitosan capsule by the Japan Pharmacopoeia (JP) rotating basket method. The release of 5-ASA from the chitosan capsule markedly increased in the presence of rat cecal contents. After oral administration of chitosan capsules containing 5-ASA, the concentrations of 5-ASA in the large intestinal mucosa were higher than those in the CMC suspension. For the treatment of colitis in rats, 5-ASA was orally administered using chitosan capsules or a carboxy methyl cellulose (CMC) suspension to TNBS-induced rats. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activities, colon wet weight/body weight (C/B) ratio and the damage score, respectively. When 5-ASA was orally administered using chitosan capsules in TNBS-induced colitis rats, we found better therapeutic effects with 5-ASA than with a 5-ASA CMC suspension, as evaluated by the MPO activities, C/B ratio and the damage score. In conclusion, chitosan capsules may be useful carriers for the colon-specific delivery of anti-inflammatory drugs including 5-ASA and the healing of TNBS-induced colitis in rats.
本研究的目的是使用壳聚糖胶囊实现抗溃疡性结肠炎药物的结肠特异性递送，并加速2,4,6-三硝基苯磺酸钠（TNBS）诱导的大鼠结肠炎的愈合。5-氨基水杨酸（5-ASA）用作抗炎药物的模型。壳聚糖胶囊的胃肠道转运通过在给大鼠口服给药后的特定时间通过剖腹术计数胃肠道腔内的胶囊数量来确定。壳聚糖胶囊在大鼠口服给药后3.5小时到达大肠。我们采用日本药典（JP）转篮法研究了5-ASA从壳聚糖胶囊中的释放情况。在存在大鼠盲肠内容物的情况下，5-ASA从壳聚糖胶囊中的释放明显增加。口服含有5-ASA的壳聚糖胶囊后，大肠黏膜中5-ASA的浓度高于羧甲基纤维素（CMC）混悬液中的浓度。为了治疗大鼠结肠炎，将5-ASA用壳聚糖胶囊或羧甲基纤维素（CMC）混悬液口服给予TNBS诱导的大鼠。分别通过测量髓过氧化物酶（MPO）活性、结肠湿重/体重（C/B）比值和损伤评分来评估结肠损伤和炎症。当在TNBS诱导的结肠炎大鼠中口服使用壳聚糖胶囊给予5-ASA时，通过MPO活性、C/B比值和损伤评分评估，我们发现5-ASA的治疗效果优于5-ASA CMC混悬液。总之，壳聚糖胶囊可能是用于包括5-ASA在内的抗炎药物结肠特异性递送以及TNBS诱导的大鼠结肠炎愈合的有用载体。
