Abstract LB186: Development of simvastatin nanoformulations using various polymers for the management of colorectal cancer

Abstract Colorectal Cancer (CRC) is one of the leading causes of cancer-related deaths globally, which highlights the need for efficient preventive measures. Simvastatin (SIM) is a drug with a repurposing potential for CRC chemoprevention. Previous studies from our lab have shown promising chemopreventive efficacy of SIM. In this study, we developed and compared the CRC chemopreventive action of 3 SIM nanoformulations: simvastatin lignin nanoparticles in combination with ferulic acid (SIM-LNPs-FA), SIM self-micro emulsifying drug delivery system nanoformulation (SIM-SMEDDS) and SIM- SMEDDS in combination with Chondroitin Sulfate (CHS) nanoformulation (SIM-SMEDDS-CHS). Specifically, SIM-LNPs-FA were prepared by dissolving the polymer and drug in a water-miscible solvent, which was added to an aqueous solution containing PVA. Formulations were optimized by varying the concentration of lignin (10 - 20 mg/mL), antisolvent PVA (1 - 2 %), polymer: antisolvent ratio, and polymer: drug ratio. SIM-SMEDDS formulations were prepared with a 1:1-1:3 w/w ratio of Smix (CapmulC8: Tween80-Transcutol HP) and loaded with different concentrations of SIM (3 - 7%). SIM-SMEDDS-CHS formulations were prepared in a 1:3 w/w ratio of SIM and CHS. All formulations were further characterized by particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency, and the data for optimized formulations is depicted in Table 1 (Some studies are underway). In vitro assessments using CRC cell lines (HT 29 and HCT 116) evaluate the nanoformulation's cytotoxicity, cellular uptake, and modulation of signaling pathways. The CRC cell line inhibitory studies using MTS assay revealed that the IC50 value of SIM decreased almost 2.6-fold when combined with FA, indicating synergistic activity. SIM-LNPs showed an IC50 of 28.8 µM in HT29 cells and 27.5 µM in HCT116 cells, compared to free SIM (64.5 µM and 40.5 µM, respectively) with p < 0.05, indicating statistical significance. Preliminary MTS studies for SIM-SMEDDS showed a 10-fold decrease in IC50 compared to free SIM. SIM-SMEDDS (6%) and SIM-SMEDDS-CHS (6%) demonstrated significant chemopreventive efficacy. This study highlights the potential of SIM nanoformulations for CRC chemoprevention. Citation Format: Mohammed Riaz Hasan Chowdhury, Hunter Payne, Leslie Kuang, Sunil Prabhu, Preshita Desai. Development of simvastatin nanoformulations using various polymers for the management of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB186.