Preparation, Pharmacokinetics, and Tissue Distribution Properties of Icariin-Loaded Stealth Solid Lipid Nanoparticles in Mice

Objective To evaluate the difference of the pharmacokinetic (PK) and tissue distribution properties in mice administrated with lyophilized icariin stealth solid lipid nanoparticles (Ica-SSLN) modified by polyethylene glycol and icariin control solution (Ica-Sol). Meanwhile, to establish a sensitive, specific, and stable HPLC method for the determination of Ica in mice plasma and various tissues. Methods Ica-SSLN was prepared by high temperature melt-cool solidification method. Particle size and Zeta potentials were measured by a ZetaPlus. After iv administration of Ica-SSLN and Ica-Sol at a single dose of 7.46 mg/kg, the blood and tissues including brain, liver, spleen, lung, heart, and kidney were collected at different time points. The obtained concentration from HPLC analysis was statistically treated to determine the PK model and the relevant PK parameters using DAS1.0. Tissue distribution studies of Ica-SSLN were carried out in Kunming mice after iv administration and compared to Ica-Sol. Results The characteristic data showed that the mean particle size of Ica-SSLN was (50.03 +/- 0.90) nm, entrapment efficiency was (71.67 +/- 1.09)%, and the particles carried negative charge, Zeta potential was (-22.77 +/- 1.89) mV. The concentration-time profiles of Ica in mice after iv administrated with Ica-SSLN and Ica-Sol were shown to fit a two-compartment open model. Compared with Ica-Sol, the t(1/2 beta) of Ica-SSLN was prolonged by seven times and the AUC was increased by four times. The levels of Ica concentration in the kidney tissues were significantly increased. In addition, compared with Ica-Sol, the relative target efficiency to kidney tissue was 79% and the relative tissue exposure was 16.95. Conclusion It demonstrates that Ica-SSLN has selective targeting to kidney tissue and the kidney targeted Ica-SSLN seems to have significant advantages and good development value.