Kaur Veerpal, Goyal Amit K, Ghosh Goutam, Chandra Si Sudam, Rath Goutam
Department of Pharmaceutics, I.S.F.College of Pharmacy, Moga, Punjab, India.
National Institute of Animal Biotechnology, Hyderabad, India.
Heliyon. 2020 Jan 30;6(1):e03125. doi: 10.1016/j.heliyon.2019.e03125. eCollection 2020 Jan.
The present study was designed to investigate the therapeutic efficacy of metal chelator and anticancer drug in the treatment of colorectal cancer (CRC). Pellets containing Phytic acid, 5- Fluorouracil (5-FU), Microcrystalline cellulose (MCC) PH 101, Hydroxypropyl Methylcellulose (HPMC) and Barium sulfate were prepared by using extrusion spheronization technique. Prepared pellets were coated with Eudragit S100 to achieve colon-specific drug delivery. Pellets were characterized for various pharmaceutical and micromeritic attributes. The in vivo therapeutic efficacy comprising of both pharmacokinetic and pharmacodynamic parameters was determined in Ehrlich ascites carcinoma (EAC) induced cancer animal model. Phytic acid and 5-FU combinations seem to exert higher cytotoxic activity via increased reactive oxygen species (ROS) level by chelating manganese. Further pharmacokinetic studies reveled approximately 50% lower C in the finished formulation, indicates lower systemic exposure to the drug. X-ray radiography ensures the localized delivery of the encapsulated drug. Histopathological studies indicated no significant local toxicity compared to the uncoated formulation. Results inferred that the proposed combination has superior anticancer activity with minimum systemic and local toxicity and it opens a new avenue in the treatment of colorectal cancer.
本研究旨在探讨金属螯合剂与抗癌药物联合治疗结直肠癌（CRC）的疗效。采用挤出滚圆法制备了含植酸、5-氟尿嘧啶（5-FU）、微晶纤维素（MCC）PH 101、羟丙基甲基纤维素（HPMC）和硫酸钡的微丸。用Eudragit S100对制备的微丸进行包衣，以实现结肠特异性给药。对微丸的各种药学和粉体学性质进行了表征。在艾氏腹水癌（EAC）诱导的癌症动物模型中测定了包括药代动力学和药效学参数在内的体内治疗效果。植酸和5-FU组合似乎通过螯合锰提高活性氧（ROS）水平，从而发挥更高的细胞毒性活性。进一步的药代动力学研究表明，最终制剂中的C约低50%，表明药物的全身暴露较低。X射线造影确保了包封药物的局部递送。组织病理学研究表明，与未包衣制剂相比，局部毒性不显著。结果推断，所提出的组合具有优异的抗癌活性，全身和局部毒性最小，为结直肠癌的治疗开辟了一条新途径。
