Pharmacokinetic Evaluation of 99mTc-radiolabeled Solid Lipid Nanoparticles and Chitosan Coated Solid Lipid Nanoparticles

Background: Solid Lipid Nanoparticles (SLNs) possess unique in vivo features such as high resistivity, bioavailability, and habitation at the target site. Coating nanoparticles with polymers such as chitosan greatly affects their pharmacokinetic behavior, stability, tissue uptake, and controlled drug delivery. The aim of this study was to prepare and evaluate the biodistribution of Tc-99m-labeled SLNs and chitosan modified SLNs in mice. Methods: Tc-99m-oxine was prepared and utilized to radiolabel pre-papered SLNs or chitosan coated SLNs. After purification of radiolabeled SLNs (Tc-99m-SLNs) and radiolabeled chitosan-coated SLNs (Tc-99m-Chi-SLNs) using Amicon filter, they were injected into BALB/c mice to evaluate their biodistribution patterns. In addition, nanoparticles were characterized using Transmission Electron Microscopy (TEM), Fourier-transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRD) and Dynamic Light Scattering (DLS). Results: Tc-99m-oxine with high radiochemical purity (RCP-100%) and stability (RCP > 97% at 24 h) was used to provide Tc-99m-SLNs and Tc-99m-Chi-SLNs with high initial RCP (100%). TEM image and DLS data suggest Tc-99m-SLNs susceptibility to aggregation. To that end, the main portion of Tc-99m-SLNs radioactivity accumulates in the liver and intestines, while Tc-99m-Chi-SLNs sequesters in the liver, intestines and kidneys. The blood radioactivity of Tc-99m-Chi-SLNs was higher than that of Tc-99m-SLNs by 7.5, 3.17 and 3.5 folds at 1, 4 and 8 h post-injection. Tc-99m-Chi-SI-Ns uptake in the kidneys in comparison with Tc-99m-SINs was higher by 37.48, 5.84 and 11 folds at 1, 4 and 8h. Conclusion: The chitosan layer on the surface of Tc-99m-Chi-SLNs reduces lipophilicity in comparison with Tc-99m-SLNs. Therefore, Tc-99m-Chi-SLNs are less susceptible to aggregation, which leads to their lower liver uptake and higher kidney uptake and blood concentration.