Chitosan nanoparticles of imatinib mesylate coated with TPGS for the treatment of colon cancer: In-vivo & in-vitro studies

Abstract

The study aimed to develop and evaluate chitosan-based nanoparticles coated with TPGS for the targeted delivery of imatinib mesylate to colon cancer cells. Particle size and zeta potential analysis were within the acceptable range for targeting colon cancer. CS-IMT-TPGS-NPs had a significant positive zeta potential of 30.4 mV, suggesting improved cellular intake. FE-SEM and TEM demonstrated that the nanoparticles appeared spherical, smooth, and did not aggregate, with a visible TPGS coating. XRD confirmed that crystalline imatinib transitioned to an amorphous state during nano formulation. In-vitro tests on HCT-116 cells demonstrated that CS-IMT-TPGS-NPs outperformed free IMT regarding cytotoxicity, apoptosis induction, cellular uptake, and cell migration inhibition. Additionally, the nanoparticles were examined in vitro using mitochondrial membrane potential, DNA fragmentation, GAPDH relative gene expression, ROS estimation, and cell cycle analysis. The effect of therapy on expected colon-associated bacterial strains was also investigated. The biocompatibility of nanoparticles was assessed by hemolysis and platelet aggregation experiments. The anti-inflammatory impact was determined using the HET-CAM test. Non-Fickian diffusion at pH 5.5 resulted in sustained in-vitro drug release, with no initial burst. In-vivo investigations using albino Wistar rats suggest pharmacokinetic properties for produced nanoparticles, whereas histopathological examinations assess acute toxicity.