Naringenin loaded solid lipid nanoparticles alleviate oxidative stress and enhance oral bioavailability of naringenin

Naringenin (Nrg) is the most abundant natural dietary flavonoid with promising anti-inflammatory potential. However, its therapeutic application is limited due to poor absorption, low bioavailability, and inability to cross physiological barriers. Herein, we designed biocompatible solid lipid nanoparticles (SLNs) to overcome these challenges and to enhance the oral bioavailability and therapeutic potential of Nrg. Nrg-loaded solid lipid nanoparticles (Nrg-SLNs) were fabricated from natural fatty acids, stearic (Nrg-SANPs), or a combination of stearic and lauric acid as binary nanoparticles (Nrg-SLNPs) by the hot melt encapsulation technique. The optimized Nrg-loaded nanoparticles exhibited a hydrodynamic diameter of 74 nm for SANPs and 91 nm for SLNPs, a zeta potential of -25 mV to -37 mV, and entrapment efficiency ranging from 79 % to 85 %. Electron paramagnetic resonance (EPR) spectroscopy indicated an in vitro radical protection factor (RPF) of 215 ± 2 × 10¹⁴ radicals/mg for Nrg-SLNPs, which was significantly higher than free Nrg and Nrg-SANPs. Almost 87 % reduction in oxidative stress was recorded with Nrg-SLNPs in a stress-induced lymphocyte model. In vivo studies using the Wistar rat model exhibited around 9-12-fold higher oral bioavailability of Nrg after nanoencapsulation in SLNs, as determined by high-performance liquid chromatography (HPLC). Whereas, hematological and histopathological analysis did not show any damage to the vital organs in vivo. This study presents Nrg-SLNPs as an efficient and biocompatible carrier to enhance the oral bioavailability and therapeutic activity of the natural flavonoids and warrants their further exploration in humans.