Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal targeting in mouse models of inflammatory bowel diseases
Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal targeting in mouse models of inflammatory bowel diseases
复制标题
DOI：
10.1016/j.jconrel.2014.03.039
复制
发表时间：
2014-06-10
影响因子：
10.8
通讯作者：
Lehr, C. -M.
中科院分区：
文献类型：
--
作者：
Ali, H.;Weigmann, B.;Lehr, C. -M.
本研究的目的是研究布地奈德负载纳米载体治疗炎症性肠病（IBD）的治疗潜力。首先，采用油包水（O/W）乳化技术将布地奈德包裹在聚乳酸-羟基乙酸（PLGA）纳米颗粒中。第二批相同的纳米颗粒另外涂有ph敏感的甲基丙烯酸甲酯共聚物。无膜PLGA和包覆PLGA的粒径分别为200 +/- 10.1 nm和240 +/- 14.7 nm。正如在体外实验中所显示的那样，pH敏感包衣可以防止药物在酸性pH下过早释放，并且仅在中性至微碱性pH下释放药物。在不同的急性和慢性结肠炎小鼠模型中评估了包衣和普通纳米颗粒制剂的功效，并与药物的水溶液进行了比较。剂量始终相同（0.168 mg/kg）。结果发现，包被的PLGA纳米颗粒递送对结肠炎的缓解效果明显优于普通PLGA颗粒递送，已优于相同剂量的游离药物治疗。这些数据进一步证实了聚合物纳米载体在炎症肠粘膜靶向药物递送方面的潜力，并且通过实现ph依赖性药物释放特性，这一概念在口服给药途径方面仍可进一步完善。(C) 2014 Elsevier B.V.版权所有
The purpose of this study was to investigate the therapeutic potential of budesonide loaded nanocarriers for the treatment of inflammatory bowel disease (IBD). First, budesonide was encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles by an oil in water (O/W) emulsion technique. A second batch of the same nanoparticles was additionally coated with a pH-sensitive methyl-methacrylate-copolymer. The particle sizes of the plain and the coated PLGA were 200 +/- 10.1 nm and similar to 240 +/- 14.7 nm, respectively. As could be shown in vitro, the pH-sensitive coating prevented premature drug release at acidic pH and only releases the drug at neutral to slightly alkaline pH. The efficacy of both coated and plain nanoparticle formulations was assessed in different acute and chronic colitis mouse models, also in comparison to an aqueous solution of the drug. The dose was always the same (0.168 mg/kg).It was found that delivery by coated PLGA nanoparticles alleviated the induced colitis significantly better than by plain PLGA particles, which was already more effective than treatment with the same dose of the free drug. These data further corroborate the potential of polymeric nanocarriers for targeted drug delivery to the inflamed intestinal mucosa, and that this concept can still be further improved regarding the oral route of administration by implementing pH-dependent drug release characteristics. (C) 2014 Elsevier B.V. All rights reserved.