The present study aimed to develop a novel colon-targeting microsphere of beclomethasone dipropionate (cMS/BDP) with enhanced pharmacological effect of BDP in the colon. cMS/BDP was prepared using Eudragit^® S-100 by the emulsion solvent diffusion method, and its physicochemical properties were characterized. A pharmacokinetic study was conducted to assess systemic exposure and colon distribution of BDP after oral administration of cMS/BDP to rats. A pharmacodynamic study was carried out to evaluate the anti-inflammatory effect of cMS/BDP after its oral administration to ulcerative colitis model rats. The particle size of cMS/BDP was calculated to be ca. 20 μm, and most BDP in cMS/BDP might be in an amorphous state. In dissolution tests, cMS/BDP showed pH-dependent release behavior of BDP and marked BDP release at pH 7.4. After oral administration of cMS/BDP (5 mg-BDP/kg) to rats, BDP was rapidly metabolized to beclomethasone 17-monopropionate (17-BMP, a BDP metabolite) in the gastrointestinal tract and liver, and relative oral bioavailability of 17-BMP in the cMS/BDP group was calculated to be ca. 4.8% compared with that in the BDP solution group. The tissue-to-plasma partition coefficient value, an index of colon distribution, for cMS/BDP was found to be 15-fold higher than that for BDP solution. In the cMS/BDP (50 μg/kg) group, colonic myeloperoxidase activity and hyperplasia of the submucosa were negligibly elevated. From these findings, the cMS approach for BDP would be a promising dosage option for strategic colon delivery, leading to an improved therapeutic potential of BDP with a wide safety margin.

Keywords: beclomethasone dipropionate; colon delivery; enteric microsphere; pharmacokinetics; ulcerative colitis.

© 2025 John Wiley & Sons Ltd.

本研究旨在开发一种新型的布地奈德磷酸二丙酯（BDP）结肠靶向微球（cMS/BDP），以增强布地奈德在结肠中的药理学效果。使用Eudragit® S-100通过乳化溶剂扩散法制备了cMS/BDP，并对其物理化学性质进行了表征。进行了一项药代动力学研究，评估口服给药后cMS/BDP对大鼠全身暴露和结肠分布的影响。一项药效学研究表明，在溃疡性结肠炎模型大鼠中口服给予cMS/BDP后的抗炎效果。cMS/BDP的粒径约为20 μm，且大部分布地奈德在cMS/BDP中可能是无定形状态。在溶解试验中，cMS/BDP表现出pH依赖性的布地奈德释放行为，并在pH 7.4时显示显著的布地奈德释放量。口服给予大鼠5 mg-BDP/kg cMS/BDP后，布地奈德迅速代谢为布地奈德单丙酸酯（17-BMP）并在胃肠道和肝脏中形成，与布地奈德溶液组相比，cMS/BDP组的相对口服生物利用度约为4.8%。组织-血浆分配系数值是结肠分布的一个指标，对于cMS/BDP而言，其值比布地奈德溶液高出15倍。在给予大鼠cMS/BDP（50 μg/kg）后，结肠髓过氧化物酶活性和粘膜下层增生可以忽略不计。根据这些发现，对于布地奈德采用cMS方法可能会是一种有前景的剂量选择方案，具有战略性的结肠递送能力，并能提高布地奈德的安全性和治疗潜力。

关键词：布地奈德磷酸二丙酯；结肠给药；包衣微球；药代动力学；溃疡性结肠炎。