Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, 500 037, India.
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
AAPS PharmSciTech. 2024 Mar 1;25(3):52. doi: 10.1208/s12249-024-02759-0.
As a major public health issue, colorectal cancer causes 9.4% of total cancer-related deaths and comprises 10% of new cancer diagnoses worldwide. In the year 2023, an estimated 153,020 people are expected to receive an identification of colorectal cancer (CRC), resulting in roughly 52,550 fatalities anticipated as a result of this illness. Among those impacted, approximately 19,550 cases and 3750 deaths are projected to occur in individuals under the age of 50. Irinotecan (IRN) is a compound derived from the chemical structure of camptothecin, a compound known for its action in inhibiting DNA topoisomerase I. It is employed in the treatment strategy for CRC therapies. Comprehensive in vivo and in vitro studies have robustly substantiated the anticancer efficacy of these compounds against colon cancer cell lines. Blending irinotecan in conjunction with other therapeutic cancer agents such as oxaliplatin, imiquimod, and 5 fluorouracil enhanced cytotoxicity and improved chemotherapeutic efficacy. Nevertheless, it is linked to certain serious complications and side effects. Utilizing nano-formulated prodrugs within "all-in-one" carrier-free self-assemblies presents an effective method to modify the pharmacokinetics and safety portfolio of cytotoxic chemotherapeutics. This review focuses on elucidating the mechanism of action, exploring synergistic effects, and innovating novel delivery approaches to enhance the therapeutic efficacy of irinotecan.
作为一个主要的公共卫生问题,结直肠癌导致 9.4%的癌症相关死亡,并占全球 10%的新癌症诊断。在 2023 年,预计将有 153020 人被诊断为结直肠癌(CRC),预计其中约有 52550 人将因此病死亡。在受影响的人群中,预计有 19550 例和 3750 例死亡发生在 50 岁以下的人群中。伊立替康(IRN)是一种从喜树碱的化学结构衍生而来的化合物,喜树碱是一种以抑制 DNA 拓扑异构酶 I 为作用机制的化合物。它被用于结直肠癌治疗策略。综合体内和体外研究强有力地证实了这些化合物对结肠癌细胞系的抗癌功效。将伊立替康与其他治疗癌症的药物如奥沙利铂、咪喹莫特和 5-氟尿嘧啶联合使用可以增强细胞毒性和提高化疗效果。然而,它与某些严重的并发症和副作用有关。在“无载体”自组装的“一体化”载体中使用纳米制剂前药是一种有效的方法,可以改变细胞毒性化疗药物的药代动力学和安全性特征。这篇综述重点阐述了伊立替康的作用机制、协同作用的探索以及创新的新型给药方法,以提高其治疗效果。