Preparation, characterization and pharmacokinetic assessment of Diosmetin solid lipid nanoparticles: A bioanalytical approach using LC-MS/MS

Diosmetin (DIO) is a flavonoid found in the peel of citrus lemon and is known for its anticancer and anti-inflammatory properties. DIO has limited solubility in water, which limits oral bioavailability. Therefore, in this research article, we aim to prepare solid lipid nanoparticles of DIO (DIO-SLNs) to improve their oral solubility and bioavailability. The new, sensitive HPLC, LC-ESI-MS/MS analytical and bioanalytical methods were optimized. The optimized batch of DIO-SLNs demonstrated particle size, zeta potential, and PDI values of 187.8 ± 4.50 nm, −23.7 ± 2.44, and 0.28 ± 0.01respectively. The entrapment efficiency of prepared nanoparticles is 99.4 ± 0.43 %. The DSC and XRD study of DIO-SLNs confirms the amorphous nature. SEM, TEM, and AFM confirm that the prepared particles are spherical with a complete round structure. In vitro, cell viability testing on the SHSY5Y cell line revealed that the prepared formulation is safe up to 3 μm, with a viability of 73.15 %. The in vitro drug release study confirms that DIO releases slowly and steadily from SLNs compared to pure DIO. The in vivo pharmacokinetic study on SD male rats was performed. The DIO-SLNs showed a 5.15-fold increase in relative bioavailability when administered orally. The C_max of pure DIO and DIO-SLNs were 0.2625 ± 0.06 and 3.55 ± 1.056 ng/mL, respectively. This work ensures that incorporating DIO into SLNs significantly enhances their solubility and bioavailability, making them suitable for functional foods and pharmaceuticals.