Makhlof Abdallah, Tozuka Yuichi, Takeuchi Hirofumi
Department of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.
Eur J Pharm Biopharm. 2009 May;72(1):1-8. doi: 10.1016/j.ejpb.2008.12.013.
Novel pH-sensitive nanospheres designed for colon-specific delivery were prepared using polymeric mixtures of poly (lactic-co-glycolic) acid (PLGA) and a pH-sensitive methacrylate copolymer. Budesonide (BSD), a topically active corticosteroid, was entrapped as a model drug. The therapeutic efficacy of the prepared nanospheres was assessed using the trinitrobenzenesulfonic acid (TNBS) colitis rat model, in comparison with conventional enteric microparticles. In addition, the colon targeting properties, systemic bioavailability, and specific uptake by the inflamed colon mucosa were evaluated using coumarin-6 (C-6)-loaded nanospheres. The prepared nanospheres showed strongly pH-dependent drug release properties in acidic and neutral pH values followed by a sustained release phase at pH 7.4. Animal experiments revealed the superior therapeutic efficiency of BSD-loaded nanospheres in alleviating the conditions of TNBS-induced colitis model. The in vivo studies using C-6-loaded nanospheres displayed higher colon levels and lower systemic availability of the fluorescent marker when compared with simple enteric coating. Moreover, quantitative analysis of the fluorescent marker and confocal laser scanning studies showed strong and specific adhesion of the nanospheres to the ulcerated and inflamed mucosal tissue of the rat colon. In conclusion, the proposed nanosphere system combined the properties of pH-sensitivity, controlled release, and particulate targeting that could be useful for colon-specific delivery in inflammatory bowel disease.
采用聚（乳酸 - 乙醇酸）共聚物（PLGA）和pH敏感型甲基丙烯酸酯共聚物的聚合物混合物制备了用于结肠特异性递送的新型pH敏感纳米球。将具有局部活性的皮质类固醇布地奈德（BSD）作为模型药物包封其中。与传统的肠溶微粒相比，使用三硝基苯磺酸（TNBS）结肠炎大鼠模型评估了所制备纳米球的治疗效果。此外，使用负载香豆素 - 6（C - 6）的纳米球评估了结肠靶向特性、全身生物利用度以及炎症结肠黏膜的特异性摄取。所制备的纳米球在酸性和中性pH值下表现出强烈的pH依赖性药物释放特性，随后在pH 7.4时进入缓释阶段。动物实验表明，负载BSD的纳米球在缓解TNBS诱导的结肠炎模型病情方面具有卓越的治疗效果。与简单的肠溶包衣相比，使用负载C - 6的纳米球进行的体内研究显示荧光标记物在结肠中的含量更高，全身利用率更低。此外，荧光标记物的定量分析和共聚焦激光扫描研究表明，纳米球与大鼠结肠溃疡和炎症黏膜组织具有强烈且特异性的粘附。总之，所提出的纳米球系统结合了pH敏感性、控释和颗粒靶向特性，可用于炎症性肠病的结肠特异性递送。
