Optimization of chitosan-PEG-geranium oil nanoparticles and in-vitro studies on pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited therapeutic options and is expected to become the second leading cause of cancer-related deaths by 2030. Geraniol, a naturally occurring monoterpenoid found in essential oils, has demonstrated anticancer activity but its clinical use is restricted by poor solubility and low bioavailability. In this study, geraniol was encapsulated within chitosan-polyethylene glycol (CS-PEG) nanocarriers using an ionic interaction method to enhance its therapeutic efficacy. Formulation parameters were optimized using a statistical design approach to evaluate the influence of polymer and surfactant concentrations on encapsulation efficiency. The optimized formulation showed strong model validity (p < 0.005; F = 6.89) and achieved an encapsulation efficiency of 93.87%. Physicochemical characterization confirmed an amorphous structure with an average particle size below 250 nm. In vitro cytotoxicity and apoptosis assessments using MTT and AO/PI assays on pancreatic cancer cell lines revealed enhanced, dose-dependent anticancer activity. The CS-PEG-geraniol nanocarriers demonstrated significantly greater efficacy at 100 µg/mL compared to free geraniol. Overall, the findings suggest that CS-PEG nanocarriers represent a promising and biocompatible delivery platform for improving geraniol-based therapy against PDAC.