Desai Neha, Momin Munira
Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Gate No. 1, SVKM Campus, V. M. Road, Vile Parle (W), Mumbai, 400 056, India.
Drug Deliv Transl Res. 2020 Oct;10(5):1288-1301. doi: 10.1007/s13346-020-00756-x.
The objective of the present work was to develop and optimize multiparticulate pH-dependent bioadhesive pellets of curcumin and cyclosporine for the management of intestinal bowel disease (IBD). The bioadhesive sustained release pellets were intended for targeting the affected site for an improved therapeutic effect. Bioadhesive pellet cores of curcumin and cyclosporine were formulated using Carbopol 940 (CP940) and hydroxypropyl cellulose (HPC-H) by the extrusion/spheronization method, and drug delivery to the colon was controlled by the pH-sensitive polymer Eudragit® S100. Microcrystalline cellulose (Avicel PH101) was found to be the best forming agent for pellet core. The ratio of CP940 to HPC-H was kept at 1:1 to achieve 100% bioadhesion. The in vitro dissolution profiles of coated pellets depicted that 12.327 ± 0.342% of curcumin and 14.751 ± 0.112% of cyclosporine were released at the end of 6 h (at pH 6.8), whereas 71.278 ± 0.100% of curcumin and 76.76 ± 0.195% of cyclosporine were released at the end of 24 h (at pH 7.4). The drug release profile was found to follow zero-order kinetics for both drugs. The selected formulation was evaluated on an acetic acid-induced ulcerative colitis in the rat model to evaluate the efficiency of drug-loaded pellets coated with Eudragit®S100. The pharmacodynamic study revealed the therapeutic efficacy of Eudragit®S100-coated pellets of curcumin and cyclosporine in alleviating the conditions of the acetic acid-induced colitis model as reflected by weight gain as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis, as compared with free curcumin and cyclosporine. The combination of curcumin and cyclosporine has been proven to have a synergistic effect for the successful management of IBD when used in a low dose as compared with individual drugs with high doses. Hence, curcumin- and cyclosporine-loaded bioadhesive pellets may act as a promising targeted drug delivery system in the management of IBD. Graphical abstract.
本研究的目的是开发并优化姜黄素和环孢素的多颗粒pH依赖型生物黏附微丸，用于治疗肠道疾病（IBD）。这种生物黏附缓释微丸旨在靶向作用于患病部位，以提高治疗效果。采用挤出/滚圆法，使用卡波姆940（CP940）和羟丙基纤维素（HPC-H）制备姜黄素和环孢素的生物黏附微丸芯，并用pH敏感聚合物Eudragit® S100控制药物向结肠的释放。发现微晶纤维素（Avicel PH101）是微丸芯的最佳成型剂。CP940与HPC-H的比例保持在1:1，以实现100%的生物黏附性。包衣微丸的体外溶出曲线表明，在6小时结束时（pH 6.8），姜黄素的释放量为12.327±0.342%，环孢素的释放量为14.751±0.112%；而在24小时结束时（pH 7.4），姜黄素的释放量为71.278±0.100%，环孢素的释放量为76.76±0.195%。两种药物的释药曲线均符合零级动力学。在大鼠乙酸诱导的溃疡性结肠炎模型上对所选制剂进行评估，以评价用Eudragit® S100包衣的载药微丸的有效性。药效学研究表明，与游离姜黄素和环孢素相比，用Eudragit® S100包衣的姜黄素和环孢素微丸在减轻乙酸诱导的结肠炎模型的症状方面具有治疗效果，这体现在体重增加以及诱导性结肠炎的临床、宏观和微观参数的改善上。与高剂量的单一药物相比，低剂量使用时，姜黄素和环孢素的组合已被证明对成功治疗IBD具有协同作用。因此，载有姜黄素和环孢素的生物黏附微丸可能是治疗IBD的一种有前景的靶向给药系统。图形摘要。
