Development and characterization of hyaluronic acid surface scaffolds Encorafenib loaded polymeric nanoparticles for colorectal cancer targeting

Abstract

For treatment of colorectal cancer and to improve intravascular bioavailability, Encorafenib (ECF) encapsulated Hyaluronic Acid (HA) decorated polycaprolactone (PCL), and polyhydroxybutyrate (PHB) polymeric nanoparticles were prepared. The DLS, SEM, and TEM data show an increase in particle size (<200 nm) after hyaluronic acid conjugation over polymeric nanoparticles. AFM confirms that HA-linked nanoparticles have a rougher surface. FTIR, DSC, XRD, and TGA confirm that HA conjugates form amorphous nanoparticles. The in-vitro drug release study indicated initial burst release of ECF followed by sustain release profile. In vitro cytotoxicity testing revealed that HA-ECF-PHB-NPs significantly inhibited HCT116 cell lines compared to the other three nanoparticles and ECF drug solutions. The genotoxicity of polymeric nanoparticles was assessed by cytokinesis-block micronucleus (CBMN) assay, indicating DNA damage in HCT116 cells and micronuclei and nuclear buds’ formation. The produced nanoparticles can lower ROS, possibly due to their good cellular internalisation and apoptotic arrest. Histopathology of colon tissue following nanoparticle injection showed no injury. Haemolysis, LDH assay showed nanoparticles' biocompatibility. According to fluorescence research, epithelial colon cells accumulate more fluorescent nanoparticles after i.v. administration. The ECF polymeric nanoparticles fabricated with HA can be considered a promising drug delivery system for colorectal cancer therapy.