PMID- 37717622 OWN - NLM STAT- MEDLINE DCOM- 20231011 LR - 20231011 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 332 DP - 2023 Nov 1 TI - Combination chemotherapy against colorectal cancer cells: Co-delivery of capecitabine and pioglitazone hydrochloride by polycaprolactone-polyethylene glycol carriers. PG - 122083 LID - S0024-3205(23)00718-X [pii] LID - 10.1016/j.lfs.2023.122083 [doi] AB - 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 (1)H 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 degrees C than 4 degrees 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. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Pouya, Fahima Danesh AU - Pouya FD AD - Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. Electronic address: daneshpouya.f@umsu.ac.ir. FAU - Salehi, Roya AU - Salehi R AD - Department of Medical Nanotechnology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Rasmi, Yousef AU - Rasmi Y AD - Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran; Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran. Electronic address: rasmiy@umsu.ac.ir. FAU - Kheradmand, Fatemeh AU - Kheradmand F AD - Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. FAU - Fathi-Azarbayjani, Anahita AU - Fathi-Azarbayjani A AD - Department of Pharmaceutical Sciences, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran. LA - eng PT - Journal Article DEP - 20230917 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - X4OV71U42S (Pioglitazone) RN - 24980-41-4 (polycaprolactone) RN - 6804DJ8Z9U (Capecitabine) RN - 0 (Antineoplastic Agents) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Humans MH - Pioglitazone/pharmacology MH - Capecitabine/pharmacology MH - *Antineoplastic Agents MH - Human Umbilical Vein Endothelial Cells MH - Polyethylene Glycols/chemistry MH - *Colorectal Neoplasms/drug therapy MH - Drug Therapy, Combination OTO - NOTNLM OT - Apoptosis OT - Capecitabine OT - Colorectal cancer OT - Combination chemotherapy OT - Micelle OT - Pioglitazone hydrochloride COIS- Declaration of competing interest The authors declare that there are no conflicts of interest. EDAT- 2023/09/18 00:41 MHDA- 2023/10/11 06:45 CRDT- 2023/09/17 19:13 PHST- 2023/07/08 00:00 [received] PHST- 2023/09/01 00:00 [revised] PHST- 2023/09/11 00:00 [accepted] PHST- 2023/10/11 06:45 [medline] PHST- 2023/09/18 00:41 [pubmed] PHST- 2023/09/17 19:13 [entrez] AID - S0024-3205(23)00718-X [pii] AID - 10.1016/j.lfs.2023.122083 [doi] PST - ppublish SO - Life Sci. 2023 Nov 1;332:122083. doi: 10.1016/j.lfs.2023.122083. Epub 2023 Sep 17.