Combination chemotherapy against colorectal cancer cells: Co-delivery of capecitabine and pioglitazone hydrochloride by polycaprolactone-polyethylene glycol carriers.

BACKGROUND: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). METHOD: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. RESULT: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. CONCLUSION:The (CAP-PGZ)-loaded TB nanoparticles in this research offer an effective strategy for targeted combinational colorectal cancer therapy.