Paroxetine HCl-Loaded Polymeric Nanoparticles for Colorectal Cancer Therapy: Optimization by Box–Behnken Design and Evaluation of Antiproliferative Efficiency on HCT-116 Cells

Abstract Purpose Colorectal cancer (CRC) continues to be one of the leading causes of cancer-related deaths, and current chemotherapeutic regimens face significant limitations such as systemic toxicity, limited tumor specificity and multidrug resistance. To overcome these limitations, the combination of drug repurposing with nanoscale drug-delivery platforms is an innovative approach to enhance therapeutic efficacy while improving safety. In this study, the antiproliferative potential of paroxetine HCl, a selective serotonin reuptake inhibitor (SSRI), is aimed to be evaluated in the context of CRC treatment through polycaprolactone (PCL) nanoparticles. Methods Paroxetine HCl-loaded polymeric nanoparticles were prepared using the double emulsion-solvent evaporation method. Formulation parameters were systematically optimized using a Box–Behnken experimental design, and the nanoparticles were characterized for their physicochemical properties. The cytotoxicity of the nanoparticles was investigated in vitro using the HCT-116 CRC cell line. Results Optimized nanoparticles exhibited an average particle size of 304.1 ± 1.76 nm, a polydispersity index of 0.143 ± 0.014 and an an encapsulation efficiency of 88%. In vitro release studies indicated a sustained release profile above 88% over 12 h. Cytotoxicity tests conducted on HCT-116 cells have revealed that the nanoparticle formulation exhibits a significantly greater antiproliferative effect than free paroxetine HCl. Conclusion The findings indicate that paroxetine HCl-loaded polymeric nanoparticles offer a promising drug-repositioning and nanocarrier strategy for the treatment of CRC. However, comprehensive in vivo and advanced preclinical studies are needed to validate the clinical applicability of this system.