Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, Minia, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; Assiut International Center of Nanomedicine, Assiut University, Assiut, Egypt; Laboratory for Synthetic-Biologic Interactions, Department of Chemistry, Texas A&M University, College Station, TX, USA.
Eur J Pharm Sci. 2017 Nov 15;109:269-279. doi: 10.1016/j.ejps.2017.08.025. Epub 2017 Aug 19.
Azathioprine is a highly efficient immunosuppressant drug used for treatment of inflammatory bowel disease (IBD). Systemic administration of azathioprine results in delayed therapeutic effect and serious adverse reactions. In the current study, we have developed, for the first time, colon-targeted chitosan beads for delivery of azathioprine in colitis rabbit model. Several characterizations were performed for the azathioprine-loaded beads (e.g. drug encapsulation efficiency, drug loading capacity, yield, size, shape and compatibility with other ingredients). The in vitro release profiles of acid-resistant capsules filled with azathioprine-loaded beads showed that most of azathioprine was released in IBD colon simulating medium. The therapeutic effects of azathioprine-loaded beads and azathioprine crude drug were examined on acetic acid-induced colitis rabbit model. Improved therapeutic outcomes were observed in the animals treated with the azathioprine-loaded beads, as compared to the untreated animal controls and the animals treated with the azathioprine free drug, based on the clinical activity score, index of tissue edema, mortality rate, colon macroscopic score and colon histopathological features. In the animals treated with the azathioprine-loaded beads, the levels of the inflammatory mediators, myeloperoxidase enzyme and tumor necrosis factor-α, were significantly reduced to levels similar to those observed in the normal rabbits. Furthermore, the activities of the antioxidant enzymes, superoxide dismutase and catalase, were restored considerably in the animals treated with the drug-loaded beads. The azathioprine-loaded beads developed in the current study might have great potential in the management of IBD.
硫唑嘌呤是一种高效的免疫抑制剂药物，用于治疗炎症性肠病（IBD）。硫唑嘌呤的全身给药会导致治疗效果延迟和严重的不良反应。在本研究中，我们首次开发了用于结肠炎兔模型中传递硫唑嘌呤的结肠靶向壳聚糖珠。对载硫唑嘌呤珠（如药物包封效率、载药量、产率、粒径、形状和与其他成分的相容性）进行了几项特征描述。耐酸胶囊中载硫唑嘌呤珠的体外释放曲线表明，大部分硫唑嘌呤在 IBD 结肠模拟介质中释放。在乙酸诱导的结肠炎兔模型中，研究了载硫唑嘌呤珠和硫唑嘌呤原料药的治疗效果。与未治疗的动物对照组和未治疗的动物对照组相比，用载硫唑嘌呤珠治疗的动物的临床活动评分、组织水肿指数、死亡率、结肠宏观评分和结肠组织病理学特征均有明显改善。在接受载硫唑嘌呤珠治疗的动物中，炎症介质髓过氧化物酶酶和肿瘤坏死因子-α的水平显著降低，与正常兔观察到的水平相似。此外，载药珠治疗的动物中抗氧化酶超氧化物歧化酶和过氧化氢酶的活性得到了相当大的恢复。本研究中开发的载硫唑嘌呤珠在 IBD 的治疗中可能具有很大的潜力。
