Development of hesperidin loaded lipid-chitosan nanoparticles: physicochemical characterization, molecular docking and ex vivo study

Abstract Hesperidin (HSP) is a bioactive flavonoid, and its activity is limited due to poor water solubility. We designed this research to develop and evaluate hesperidin nanoparticles (HSPNPs) to enhance drug release and therapeutic efficacy. HSPNPs were prepared by the magnetic stirring and probe sonication techniques using the glyceryl monostearate, chitosan, poloxamer 188 and D- α-tocopheryl polyethylene glycol succinate. The developed HSPNPs were characterized for the particle size (PS), surface charge (ZP), encapsulation efficiency (EE), drug load (DL), and other physicochemical assessments. Finally, the optimized HSPNPs2 was further evaluated for in-vitro dissolution, antioxidant, anti-inflammatory activities, as well as an ex-vivo permeation study. The results were supported by the findings of a molecular docking study on the anti-inflammatory (iNOS oxygenase) and antioxidant receptors (glutathione transferase and superoxide dismutase). HSPNPs displayed the PS between 175 and 275 nm, PDI values ˂0.05, ZP (˃ 20 mV), EE (69.9 ± 3.8 to 90.3 ± 5.3%), DL (7.2 ± 0.8 to 9.5 ± 1.1%) and a prolonged drug release (71.1 ± 4.6% in 24 h) with Higuchi release order kinetics. DSC and XRD studies reveal the conversion of crystalline HSP into an amorphous form. The in vitro antioxidant and anti-inflammatory results showed concentration-dependent activity. An excellent molecular docking score was observed for antioxidant (-5.41 kcal/mole for GSH and − 5.15 kcal/mole for SOD) and anti-inflammatory (-5.85 kcal/mole for iNOS) receptors. Based on the results, we can say that the GMS- and CHT-based nanoparticles could be a beneficial way to deliver HSP by oral route so that its solubility can be enhanced and it exhibits better biological effects.