Genistein encapsulated inulin-stearic acid bioconjugate nanoparticles: Formulation development, characterization and anticancer activity

Achieving controlled and site-specific delivery of hydrophobic drugs in the colon environment is a major challenge. The primary goal of this research was to synthesize inulin-stearic acid (INU-SA) conjugate and to evaluate its potential in the site-specific delivery of genistein (GEN) for the treatment of colon cancer. INU is a hydrophilic polysaccharide biological macromolecule was modified with hydrophobic SA to form amphiphilic conjugate (INU-SA) which can self-assemble into spherical nanoparticles with interesting drug release properties. The hydrophobic GEN was encapsulated into the INU-SA conjugate to prepare GEN loaded nanoparticles (GNP). The prepared GNP possessed nano size (115 nm), good colloidal dispersibility (0.066 PDI), and high drug encapsulation efficiency (92.2%). The release behaviour of GNP indicated the site-specific release of GEN, only 3.4% at gastric pH while 94% at intestinal pH. The prepared GNP showed potential cytotoxicity against HCT 116 human colorectal cancer cells, as demonstrated by antiproliferation and apoptosis assays. The observed half maximum inhibitory concentration (IC₅₀) value of GNP (5.5 μg/mL) was significantly lower than pure GEN (28.2 μg/mL) due to higher cellular internalization of GNP than free GEN. Therefore, this research suggests a way to improve the therapeutic effectiveness of natural biomolecules using modified and biocompatible polysaccharide INU.