大肠癌尽管存在多种治疗选择，仍然导致许多死亡病例。卡培他滨（CAP）是大肠癌的标准化疗方案，而派格列酮盐酸盐（PGZ）用于糖尿病治疗。然而，单独的药物无法有效诱导细胞凋亡。本研究旨在共包装CAP和PGZ，并评估对HCT-119、HT-29大肠癌细胞和人脐静脉内皮细胞（HUVECs）的细胞毒作用和凋亡效应。CAP、PGZ和联合治疗的纳米制剂由三嵌段（TB）（PCL-PEG-PCL）生物可降解共聚物制备，以增强这些药物作为抗癌药物的生物利用度。超声波均匀化法用于制备纳米颗粒。使用1H核磁共振、傅里叶变换红外光谱、动态激光散射和场发射扫描电子显微镜技术研究了纳米颗粒的理化特性。研究了纳米颗粒的ζ电位、封装效率、药物释放和贮存稳定性。此外，通过MTT、吖啶橙（AO）和碘化丙啶（PI）检测细胞存活率和凋亡率。纳米颗粒显示较小的流体力学尺寸（236.1 nm），多分散性指数（0.159）和ζ电位（-20.8 mV）。与4℃相比，纳米颗粒在25℃下显示了更好的配方和贮存稳定性，可持续90天。在HUVEC、HCT-116和HT-29细胞中观察到（CAP-PGZ）负载的TB纳米颗粒具有协同作用。在（AO/PI）染色中，HUVEC、HCT-116和HT-29中的（CAP-PGZ）负载的TB纳米颗粒的凋亡细胞比例分别为78％、71.66％和69.31％。本研究中的（CAP-PGZ）负载的TB纳米颗粒提供了一种有效的结合靶向大肠癌治疗策略。版权所有 © 2023。由Elsevier Inc.出版。

Colorectal cancer causes numerous deaths despite many treatment options. Capecitabine (CAP) is the standard chemotherapy regimen for colorectal cancer, and pioglitazone hydrochloride (PGZ) for diabetic disease treatment. However, free drugs do not induce effective apoptosis. This work aims to co-encapsulate CAP and PGZ and evaluate cytotoxic and apoptotic effects on HCT-119, HT-29 colorectal cancer cells, and human umbilical vein endothelial cells (HUVECs).CAP, PGZ, and combination treatment nano-formulations were prepared by triblock (TB) (PCL-PEG-PCL) biodegradable copolymers to enhance drugs' bioavailability as anti-cancer agents. The Ultrasonic homogenization method was used for preparing nanoparticles. The physicochemical characteristics of nanoparticles were studied using 1H NMR, FTIR, DLS, and FESEM techniques. The zeta potential, entrapment efficiency, drug release, and storage stability were studied. Also, cell viability and apoptosis were examined by using MTT, acridine orange (AO), and propidium iodide (PI), respectively.The smaller hydrodynamic size (236.1 nm), polydispersity index (0.159), and zeta potential (-20.8 mV) were observed in nanoparticles. Nanoparticles revealed a proper formulation and storage stability at 25 °C than 4 °C in 90 days. The synergistic effect was observed in (CAP-PGZ)-loaded TB nanoparticles in HUVEC, HCT-116, and HT-29 cells. In (AO/PI) staining, the high percentage of apoptotic cells in the (CAP-PGZ)-loaded TB nanoparticles in HUVEC, HCT-116, and HT-29 were calculated as 78 %, 71.66 %, and 69.31 %, respectively.The (CAP-PGZ)-loaded TB nanoparticles in this research offer an effective strategy for targeted combinational colorectal cancer therapy.Copyright © 2023. Published by Elsevier Inc.