Abstract
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