Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 3 2026 09 30 Dual-Loaded Curcumin-Metformin Niosomes: Physicochemical Characterization and In Vitro Activity in Colorectal and Pancreatic Cancer Cells 537 549 10.34172/apb.46556 EN Aboalhasan Al-Yaqoobi https://orcid.org/0009-0000-7001-967X Sina Matalqah https://orcid.org/0000-0002-2101-3420 Zainab Lafi https://orcid.org/0000-0003-2847-2416 Anas Abed Sara Al-Mahamid Journal Article 10.34172/apb.46556 2025 10 12 2026 06 23 Purpose: Colorectal cancer and pancreatic cancer represent some of the most aggressive forms of cancer. Curcumin (CUR) and Metformin (MET) have distinct pharmacokinetic profiles. MET is water-soluble, whereas CUR is highly lipophilic. These differences in their kinetic behavior may limit their synchronized therapeutic activity when used in combination. This study aimed to develop and characterize dual-loaded curcumin–MET niosomes (NIO-CUR-MET) and evaluate their physicochemical properties, drug release behavior, and in vitro anticancer, apoptotic, and anti-inflammatory effects against HCT-116 (colorectal) and PANC-1 (pancreatic) cancer cell lines. Methods: Niosomes were prepared using the ethanol injection method and characterized using dynamic light scattering. Drug loading efficiency was determined by HPLC. Drug release was assessed over 72 hours using a dialysis method at 37°C. Anticancer activity was evaluated using the MTT assay, apoptosis via Caspase-3/7 analysis, and anti-inflammatory effects by measuring TNF-α and IL-1β levels using ELISA. Results: The particle size of 152.7±54 nm, and zeta potential of −12±1.3 mV, indicating a stable and uniform nanosystem. Encapsulation efficiencies were achieved for MET (91.5%±5%) and CUR (39.8%±7%). Release was observed ~95% for CURand ~92% for MET over 72 hours. The NIO-CUR-MET formulation significantly enhanced cytotoxicity compared to free and single-drug forms, with lower IC₅₀ values in HCT-116 (4±3.2 µM for CUR and 190±10.2 µM for MET) and PANC-1 cells IC₅₀ values (5.2±0.9 µM for CUR and 202.5±8.2 µM for MET). It also induced a 5.3-fold increase in apoptosis (P<0.001). Conclusion: Dual-loaded niosomes improved drug delivery performance and exhibited enhanced therapeutic efficacy against target cancer cell lines