Liposomal co-formulation of Azure A and rose bengal decyl ester as a multi-cellular target approach for photodynamic therapy of colorectal cancer

Multidrug systems offer a promising strategy to improve the efficacy of anticancer treatments, reduce therapeutic doses, and attenuate side effects. In this study, the photosensitizers Azure A (AA) and rose bengal decyl ester (RBDEC) were co-encapsulated in hybrid DPPC/F127 liposomes to target multiple cellular sites. The combined system yielded small unilamellar vesicles (SUVs) with a polydispersity index suitable for biological applications and a zeta potential of +10.57 mV. The encapsulation efficiency of AA and RBDEC is 60.3 and 98.5 %, respectively. In the colorectal adenocarcinoma Caco-2 cells line, photosensitizers showed distinct cellular localization, with RBDEC most targeting the nuclear region and AA the cytoplasm confirmed by confocal microscopy. According to the Chou–Talalay method for drug combinations, the equimolar and lower concentrations (2.5 × 10⁻⁶ mol L⁻¹ each) exhibited an additive effect, suggesting that even lower concentrations could achieve synergism. The findings indicate that this system exhibits considerable promise, as the combination of drugs facilitates action at multiple sites, thereby increasing the likelihood of cell death. In addition, the system demonstrated greater efficiency at lower concentrations, reducing adverse effects and directing future studies.