Department of Pharmaceutical Technology, Faculty of Pharmacy, Horus University, New Damietta, Eygpt.
Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia, Egypt.
Drug Des Devel Ther. 2020 Feb 19;14:677-696. doi: 10.2147/DDDT.S218357. eCollection 2020.
Naringin is a promising anti-inflammatory drug against various disorders including ulcerative colitis. However, its oral bioavailability is low (8%) possibly due to cleavage at the upper gut. Consequently, colon targeting would be necessary for drug protection at the upper gut, enhanced oral bioavailability and potentiated cytoprotection against colitis.
This study involved the formulation of compression-coated tablets of naringin employing mixtures of pH-sensitive Eudragit L100-55 (EUD-L100-55) and different time-dependent polymers including ethyl cellulose (EC), sodium alginate (ALG) and sodium carboxymethyl cellulose (SCMC). Drug-polymer interaction during release was assessed using Fourier transform-infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Tablets were evaluated in vitro. Surface morphology of the optimized tablets either before or after exposure to the different release media was examined employing scanning electron microscopy (SEM). Cytoprotection potential of the optimized tablets against indomethacin-induced colitis in rabbits was screened and compared to core tablets through a histopathological examination of colon, measurement of serum perinuclear antineutrophil cytoplasmic antibodies (pANCA) and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α).
FT-IR and DSC results may indicate drug-polymers interaction during release. Release retardation could be related to polymer swelling that was in the order of SCMC > ALG > EC. SEM examination indicated more porous coats at the buffers relative to the acidic medium. Colon targeting was expected in case of coats of 5% ALG, 5% SCMC and 10% EC (w/w) in combination with EUD-L100-55; thus, they were selected for in vivo evaluation. Effective cytoprotection of selected tablets against indomethacin-induced colitis was indicated by a significant (<0.05) reduction in mucosal damage, serum levels of pANCA and TNF-α expression compared to untreated colitis and core-pretreated groups. Compared to EC, higher cytoprotection potential of ALG- and SCMC-based tablets was reflected by lower concentration (5% w/w) to provide cytoprotection against indomethacin-induced colitis.
柚皮苷是一种有前途的抗炎药物，可用于治疗包括溃疡性结肠炎在内的多种疾病。然而，其口服生物利用度较低（8%），可能是由于在上消化道被分解。因此，为了在上消化道保护药物、提高口服生物利用度和增强对结肠炎的细胞保护作用，需要对结肠进行靶向给药。
本研究采用 pH 敏感型 Eudragit L100-55（EUD-L100-55）与不同时控型聚合物（包括乙基纤维素（EC）、海藻酸钠（ALG）和羧甲基纤维素钠（SCMC））混合物，对柚皮苷进行压缩包衣片剂的配方设计。采用傅里叶变换红外光谱（FT-IR）和差示扫描量热法（DSC）评估药物-聚合物在释放过程中的相互作用。对体外释放的片剂进行评价。采用扫描电子显微镜（SEM）观察优化后的片剂在暴露于不同释放介质前后的表面形态。通过对兔吲哚美辛诱导结肠炎的组织病理学检查、血清核周抗中性粒细胞胞浆抗体（pANCA）的测定以及肿瘤坏死因子-α（TNF-α）的免疫组织化学定位，筛选并比较优化后的片剂与核心片剂的细胞保护潜力。
FT-IR 和 DSC 结果可能表明药物-聚合物在释放过程中的相互作用。释放延迟可能与聚合物溶胀有关，溶胀程度顺序为 SCMC>ALG>EC。SEM 检查表明，在缓冲液中的涂层比在酸性介质中的更具多孔性。如果 5%ALG、5%SCMC 和 10%EC（w/w）的涂层与 EUD-L100-55 结合使用，则有望实现结肠靶向；因此，选择它们进行体内评价。与未治疗的结肠炎和核心预处理组相比，选定的片剂对吲哚美辛诱导的结肠炎具有有效的细胞保护作用，表现为黏膜损伤、血清 pANCA 水平和 TNF-α表达显著降低（<0.05）。与 EC 相比，基于 ALG 和 SCMC 的片剂具有更高的细胞保护潜力，其细胞保护作用可在较低浓度（5%w/w）下发挥，以对抗吲哚美辛诱导的结肠炎。
